Therapeutic combinations of orally administered docetaxel and a p-gp inhibitor for the treatment of cancer

ABSTRACT

The present disclosure provides pharmaceutical combinations of orally administered docetaxel and a P-gp inhibitor. The pharmaceutical combinations are suitable for the treatment of cancer in a subject and for reducing or preventing toxicity, hypersensitivity-type infusion reactions, and other negative outcomes resulting from or associated with intravenously administered docetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy in a subject suffering from cancer.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.17/083,543, filed on Oct. 29, 2020, which is a continuation of U.S.application Ser. No. 16/715,735, filed on Dec. 16, 2019 (now U.S. Pat.No. 10,849,893, issued on Dec. 1, 2020), which claims priority to, andthe benefit of, U.S. Provisional Application No. 62/779,742, filed onDec. 14, 2018, and 62/846,869, filed on May 13, 2019, the contents ofeach of which are incorporated herein in their entirety.

BACKGROUND

Docetaxel (Taxotere®) was approved for medical use in 1995 and marketedunder the brand name Taxotere®. Docetaxel stabilizes microtubules in thecell, thereby interfering with the normal breakdown of microtubulesduring mitosis. Docetaxel is indicated to treat many types of cancer,including lung, ovarian, and breast. However, the affinity of docetaxelfor the p-glycoprotein pump (P-gp) leads to efflux of docetaxel backinto the intestinal lumen, thus making the drug non-bioavailable whentaken orally. Its poor absorption through the intestinal epithelium,along with its unfavorable solubility, has necessitated intravenousadministration of docetaxel. Excipients, such as polysorbate 80 (Tween80®), used for intravenous administration of docetaxel often causetolerability problems such as hypersensitivity-type infusion reactions.Intravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) requires premedication which has its ownset of side effects. Further, intravenously administered docetaxel mayalso be associated with increased incidence or severity ofneurotoxicity.

Therefore, an effective therapeutic regimen including an oralformulation of docetaxel along with oral administration of a P-gpinhibitor may be beneficial, and may be expected to improve thetreatment outcomes of cancer. By inhibiting the efflux of docetaxel byP-gp back to the intestinal lumen, oral administration would allowtherapeutically relevant concentrations of the drug that are nowefficacious and also would avoid the use of excipients such aspolysorbate 80, thus leading to a wide therapeutic window that willpromote antitumor response while mitigating or avoiding the reactionsand toxicities associated directly with the drug or the excipients. Inaddition, oral administration of docetaxel provides a more convenientand safe method. The present disclosure addresses the needs for orallyadministering docetaxel.

SUMMARY

In some aspects, the present disclosure provides, at least in part,methods for treating a disease or disorder, such as cancer, or reducingor preventing toxicity, hypersensitivity-type infusion reactions and/orother negative outcomes (e.g., skin toxicity, nausea, vomiting,diarrhea, fatigue, sensory neuropathy, and infection) resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject.

In some aspects, the present disclosure provides a compound for use inthe treatment of a disease or disorder in a subject in need thereof,wherein the compound is Compound A:

In some aspects, the present disclosure provides Compound A for use inthe treatment of cancer in a subject in need thereof.

In some aspects, the present disclosure provides Compound A for use inreducing hematologic toxicity and/or neurotoxicity, and/or othertoxicities or symptoms (e.g., skin toxicity, nausea, vomiting, diarrhea,fatigue, sensory neuropathy, and infection) in a subject in needthereof.

In some aspects, the present disclosure provides Compound A for use inreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject in needthereof.

In some aspects, the present disclosure provides a method for treating adisease or disorder in a subject in need thereof, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m² to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day and for1-7 times a week, wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some aspects, the present disclosure provides a method for treatingcancer in a subject in need thereof, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m² to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day and for1-7 times a week, wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some aspects, the present disclosure provides a method for reducinghematologic toxicity and/or neurotoxicity, and/or other toxicities orsymptoms (e.g., skin toxicity, nausea, vomiting, diarrhea, fatigue,sensory neuropathy, and infection) in a subject in need thereof,comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m2 to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day and for1-7 times a week, wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some aspects, the present disclosure provides a method for reducingor preventing hypersensitivity-type infusion reactions associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject in need thereof,comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m2 to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day and for1-7 times a week, wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some aspects, the present disclosure provides use of oral docetaxelin combination with Compound A in treating a disease or disorder in asubject in need thereof.

In some aspects, the present disclosure provides use of oral docetaxelin combination with Compound A in treating cancer in a subject in needthereof.

In some aspects, the present disclosure provides use of oral docetaxelin combination with Compound A in reducing hematologic toxicity and/orneurotoxicity, and/or other toxicities or symptoms (e.g., skin toxicity,nausea, vomiting, diarrhea, fatigue, sensory neuropathy, and infection)in a subject in need thereof.

In some aspects, the present disclosure provides use of oral docetaxelin combination with Compound A in reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for oraladministration for use in combination with Compound A in treating adisease or disorder in a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for oraladministration for use in combination with Compound A in treating cancerin a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for oraladministration for use in combination with Compound A in reducinghematologic toxicity and/or neurotoxicity, and/or other toxicities orsymptoms (e.g., skin toxicity, nausea, vomiting, diarrhea, fatigue,sensory neuropathy, and infection) in a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for oraladministration for use in combination with Compound A in reducing orpreventing hypersensitivity-type infusion reactions associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides the use of docetaxel incombination with Compound A in the manufacture of a medicament fortreating a disease or disorder in a subject in need thereof.

In some aspects, the present disclosure provides the use of docetaxel incombination with Compound A in the manufacture of a medicament fortreating cancer in a subject in need thereof.

In some aspects, the present disclosure provides the use of docetaxel incombination with Compound A in the manufacture of a medicament forreducing hematologic toxicity and/or neurotoxicity, and/or othertoxicities or symptoms (e.g., skin toxicity, nausea, vomiting, diarrhea,fatigue, sensory neuropathy, and infection) in a subject in needthereof.

In some aspects, the present disclosure provides the use of docetaxel incombination with Compound A in the manufacture of a medicament forreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject in needthereof.

In some aspects, the present disclosure provides the use of docetaxelfor oral administration in combination with Compound A in themanufacture of a medicament for treating a disease or disorder in asubject in need thereof.

In some aspects, the present disclosure provides the use of docetaxelfor oral administration in combination with Compound A in themanufacture of a medicament for treating cancer in a subject in needthereof.

In some aspects, the present disclosure provides the use of docetaxelfor oral administration in combination with Compound A in themanufacture of a medicament for reducing hematologic toxicity and/orneurotoxicity, and/or other toxicities or symptoms (e.g., skin toxicity,nausea, vomiting, diarrhea, fatigue, sensory neuropathy, and infection)in a subject in need thereof.

In some aspects, the present disclosure provides the use of docetaxelfor oral administration in combination with Compound A in themanufacture of a medicament for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for use withCompound A in a combinational therapy for treating a disease or disorderin a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for use withCompound A in a combinational therapy for treating cancer in a subjectin need thereof.

In some aspects, the present disclosure provides docetaxel for use withCompound A in a combinational therapy for reducing hematologic toxicityand/or neurotoxicity, and/or other toxicities or symptoms (e.g., skintoxicity, nausea, vomiting, diarrhea, fatigue, sensory neuropathy, andinfection) in a subject in need thereof.

In some aspects, the present disclosure provides docetaxel for use withCompound A in a combinational therapy for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides Compound A for use in acombination therapy with docetaxel in the treatment of a disease ordisorder in a subject in need thereof.

In some aspects, the present disclosure provides Compound A for use in acombination therapy with docetaxel in the treatment of cancer in asubject in need thereof.

In some aspects, the present disclosure provides Compound A for use in acombination therapy with docetaxel in reducing hematologic toxicityand/or neurotoxicity, and/or other toxicities or symptoms (e.g., skintoxicity, nausea, vomiting, diarrhea, fatigue, sensory neuropathy, andinfection) in a subject in need thereof.

In some aspects, the present disclosure provides Compound A for use in acombination therapy with docetaxel in reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides use of Compound A inthe manufacture of a medicament for use in combination with docetaxel intreating a disease or disorder in a subject in need thereof.

In some aspects, the present disclosure provides use of Compound A inthe manufacture of a medicament for use in combination with docetaxel intreating cancer in a subject in need thereof.

In some aspects, the present disclosure provides use of Compound A inthe manufacture of a medicament for use in combination with docetaxel inreducing hematologic toxicity and/or neurotoxicity, and/or othertoxicities or symptoms (e.g., skin toxicity, nausea, vomiting, diarrhea,fatigue, sensory neuropathy, and infection) in a subject in needthereof.

In some aspects, the present disclosure provides use of Compound A inthe manufacture of a medicament for use in combination with docetaxel inreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject in needthereof.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with docetaxel in the treatment of a disease ordisorder in a subject in need thereof, wherein the medicament comprisesCompound A.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with docetaxel in the treatment of cancer in asubject in need thereof, wherein the medicament comprises Compound A.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with docetaxel for reducing hematologic toxicityand/or neurotoxicity, and/or other toxicities or symptoms (e.g., skintoxicity, nausea, vomiting, diarrhea, fatigue, sensory neuropathy, andinfection) in a subject in need thereof, wherein the medicamentcomprises Compound A.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof, wherein themedicament comprises Compound A.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with Compound A in the treatment of a disease ordisorder in a subject in need thereof, wherein the medicament comprisesdocetaxel.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with Compound A in the treatment of cancer in asubject in need thereof, wherein the medicament comprises docetaxel.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with Compound A for reducing hematologic toxicityand/or neurotoxicity, and/or other toxicities or symptoms (e.g., skintoxicity, nausea, vomiting, diarrhea, fatigue, sensory neuropathy, andinfection) in a subject in need thereof, wherein the medicamentcomprises docetaxel.

In some aspects, the present disclosure provides a medicament for use ina combination therapy with Compound A for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof, wherein themedicament comprises docetaxel.

In some aspects, the present disclosure provides use of Compound A in acombination therapy with docetaxel in the treatment of a disease ordisorder in a subject in need thereof.

In some aspects, the present disclosure provides use of Compound A in acombination therapy with docetaxel in the treatment of cancer in asubject in need thereof.

In some aspects, the present disclosure provides use of Compound A in acombination therapy with docetaxel for reducing hematologic toxicityand/or neurotoxicity, and/or other toxicities or symptoms (e.g., skintoxicity, nausea, vomiting, diarrhea, fatigue, sensory neuropathy, andinfection) in a subject in need thereof.

In some aspects, the present disclosure provides use of Compound A in acombination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof.

In some aspects, the present disclosure provides a pharmaceuticalcombination of docetaxel and Compound A.

In some aspects, the methods, compounds (i.e., Compound A or docetaxel)for use, use (i.e., use of Compound A or docetaxel), medicament,manufacture of medicament, medicament for use, combination, orcombination therapy, or the like, described herein, comprisesadministering orally or oral administration of Compound A, according tothe dosage and/or dosing regimen described herein (e.g., once a day andfor 1-7 times a week).

In some aspects, the methods, compounds (i.e., Compound A or docetaxel)for use, use (i.e., use of Compound A or docetaxel), medicament,manufacture of medicament, medicament for use, combination, orcombination therapy, or the like, described herein, comprisesadministering orally or oral administration of docetaxel, according tothe dosage and/or dosing regimen described herein (e.g., at an amount ofabout 15 mg/m² to about 450 mg/m² to the subject once a day and for 1-7times a week).

In some aspects, the methods, compounds (i.e., Compound A or docetaxel)for use, use (i.e., use of Compound A or docetaxel), medicament,manufacture of medicament, medicament for use, combination, orcombination therapy, or the like, described herein, comprisesadministering orally or oral administration of Compound A, according tothe dosage and/or dosing regimen described herein (e.g., once a day andfor 1-7 times a week), simultaneously with or prior to, administeringorally or oral administration of docetaxel, according to the dosageand/or dosing regimen described herein (e.g., at an amount of about 15mg/m² to about 450 mg/m² to the subject once a day and for 1-7 times aweek).

In some aspects, in the methods, compounds (i.e., Compound A ordocetaxel) for use, use (i.e., use of Compound A or docetaxel),medicament, manufacture of medicament, medicament for use, combination,or combination therapy, or the like, described herein, the subject issuffering from cancer and undergoing a docetaxel therapy.

In some aspects, in the methods, compounds (i.e., Compound A ordocetaxel) for use, use (i.e., use of Compound A or docetaxel),medicament, manufacture of medicament, medicament for use, combination,or combination therapy, or the like, described herein, the plasmaexposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 30 mg/m² to 100 mg/m² over a period of about 1 hour to about 24hours once every three weeks, once every two weeks, or once every week.

In some aspects, in the methods, compounds (i.e., Compound A ordocetaxel) for use, use (i.e., use of Compound A or docetaxel),medicament, manufacture of medicament, medicament for use, combination,or combination therapy, or the like, described herein, the orallyadministered docetaxel reaches therapeutic blood or plasma levels in thesubject.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure belongs. In the specification, thesingular forms also include the plural unless the context clearlydictates otherwise. Although methods and materials similar or equivalentto those described herein can be used in the practice or testing of thepresent disclosure, suitable methods and materials are described below.All publications, patent applications, patents and other referencesmentioned herein are incorporated by reference. The references citedherein are not admitted to be prior art to the present disclosure. Inthe case of conflict, the present specification, including definitions,will control. In addition, the materials, methods, and examples areillustrative only and are not intended to be limiting.

Other features and advantages of the present disclosure will be apparentfrom the following detailed descriptions and claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph showing the comparison of IV docetaxel and oraldocetaxel (Mean Plasma Concentration (ng/mL) vs Time (hr)) from 0 to 24hours.

FIG. 2 is a graph showing the comparison of IV docetaxel and oraldocetaxel (Mean Plasma Concentration (ng/mL) vs Time (hr)).

FIGS. 3A-3D are graphs showing the target concentration comparison forvarious IV docetaxel Regimens (35 mg/m², 75 mg/m², or 100 mg/m², eachQ3W) for 0 to 25 hours (FIG. 3A and FIG. 3B) and for 0 to 500 hours(FIG. 3C and FIG. 3D).

FIG. 4 is a graph showing the comparison of 30 mg oral docetaxel capsulestudy versus 75 mg IV docetaxel in Study 1.

FIG. 5 is a graph showing the comparison of 30 mg oral docetaxel capsulestudy versus 75 mg IV Docetaxel in Study 1.

FIGS. 6A-6D are graphs showing the Study 2 oral docetaxel concentration(ng/mL) versus time (hours) by subject per cohort; A) 35 mg/m² oraldocetaxel (cohort 1); B) 75 mg/m2 oral docetaxel (cohort 2); C) 150mg/m² oral docetaxel (cohort 3); D) 225 mg/m² oral docetaxel (cohort 4).

FIG. 7 is a graph showing the comparison of increasing oral docetaxelconcentration with increasing dose by cohort (Study 2).

FIG. 8 is a graph showing the comparison of increasing docetaxelconcentration with increasing dose (35 mg/m², 75 mg/m², 150 mg/m², 225mg/m²) by cohort, dose normalized (Study 2).

FIG. 9 is a graph showing the comparison of dose normalized docetaxelconcentration (ng/mL)/dose (mg/m²) versus time (hours), grouped bysubject and cohort from 0-24 hours (Study 2).

FIG. 10 is a graph showing the comparison of dose normalized docetaxelconcentration (ng/mL)/dose (mg/m²) versus time (hours), grouped bysubject and cohort from 0-168 hours (Study 2).

FIGS. 11A-11B are graphs showing the comparison of oral docetaxelAUC_(inf) (ng*hr/mL) versus dose (mg/m²); A) AUC_(inf) versus dose andB) AUC_(inf) versus dose, dose normalized (Study 2).

FIGS. 12A-12B are graphs showing the comparison of oral docetaxelC_(mac)(ng/mL) versus dose (mg/m²); A) C_(max) versus dose and B)C_(max) versus dose, dose normalized (Study 2).

DETAILED DESCRIPTION

In some embodiments, the present disclosure pertains, at least in part,to methods for treating cancer in a subject.

In some embodiments, the present disclosure pertains, at least in part,to methods for reducing or preventing toxicity, hypersensitivity-typeinfusion reactions, and other negative outcomes resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer.

In some embodiments, the present disclosure provides a method fortreating cancer in a subject in need thereof, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m² to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A;

to the subject once a day and for 1-7 times a week, wherein Compound Ais administered simultaneously with or prior to the docetaxel.

In some embodiments, the present disclosure provides a method forreducing hematologic toxicity and/or neurotoxicity, and/or othertoxicities or symptoms (e.g., skin toxicity, nausea, vomiting, diarrhea,fatigue, sensory neuropathy, and infection) in a subject suffering fromcancer and undergoing a docetaxel therapy, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m2 toabout 450 mg/m2 to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day and for1-7 times a week, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 30 mg/m² to 100 mg/m² over aperiod of about 1 hour to about 24 hours once every three weeks, onceevery two weeks, or once every week, and wherein Compound A isadministered simultaneously with or prior to the docetaxel.

In some embodiments, the present disclosure provides a method forreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject in needthereof, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m2 to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A to the subject once a day for 1-7times a week, wherein Compound A is administered simultaneously with orprior to the docetaxel.

In some embodiments, the present disclosure pertains, at least in part,to Compound A for use with docetaxel in the treatment of cancer in asubject.

In some embodiments, the present disclosure pertains, at least in part,to Compound A for use with docetaxel in reducing or preventing toxicity,hypersensitivity-type infusion reactions, and other negative outcomesresulting from or associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject suffering from cancer.

In some embodiments, the present disclosure provides Compound A for usewith docetaxel in the treatment of cancer in a subject in need thereof,wherein the subject is administered docetaxel orally at an amount ofabout 15 mg/m² to about 450 mg/m² once a day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day and for 1-7times a week; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides Compound A for usewith docetaxel in reducing hematologic toxicity and/or neurotoxicity,and/or other toxicities or symptoms (e.g., skin toxicity, nausea,vomiting, diarrhea, fatigue, sensory neuropathy, and infection) in asubject suffering from cancer and undergoing docetaxel therapy, whereinthe subject is administered docetaxel orally at an amount of about 15mg/m² to about 450 mg/m2 once a day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day and for 1-7times a week; and

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week, and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the present disclosure provides Compound A for usewith docetaxel in reducing or preventing hypersensitivity-type infusionreactions associated with intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) therapy in asubject in need thereof, wherein the subject is administered docetaxelorally at an amount of about 15 mg/m² to about 450 mg/m² once a day andfor 1-7 times a week;

wherein Compound A is administered to the subject once a day for 1-7times a week; and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the present disclosure pertains, at least in part,to the use of Compound A in the manufacture of a medicament for use withdocetaxel in the treatment of cancer in a subject.

In some embodiments, the present disclosure pertains, at least in part,to the use of Compound A in the manufacture of a medicament for use withdocetaxel in reducing or preventing toxicity, hypersensitivity-typeinfusion reactions, and other negative outcomes resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer.

In some embodiments, the present disclosure provides the use of CompoundA in the manufacture of a medicament for use with docetaxel in treatingcancer in a subject in need thereof, wherein the subject is administereddocetaxel orally at an amount of about 15 mg/m² to about 450 mg/m² oncea day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day and for 1-7times a week, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides the use of CompoundA in the manufacture of a medicament for use with docetaxel in reducinghematologic toxicity and/or neurotoxicity, and/or other toxicities orsymptoms (e.g., skin toxicity, nausea, vomiting, diarrhea, fatigue,sensory neuropathy, and infection) in a subject suffering from cancerand undergoing docetaxel therapy, wherein the subject is administereddocetaxel orally at an amount of about 15 mg/m² to about 450 mg/m² oncea day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day and for 1-7times a week; and

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides the use of CompoundA in the manufacture of a medicament for use with docetaxel in reducingor preventing hypersensitivity-type infusion reactions associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject in need thereof,wherein the subject is administered docetaxel orally at an amount ofabout 15 mg/m² to about 450 mg/m2 once a day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day for 1-7times a week; and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the present disclosure pertains, at least in part,to use of Compound A with docetaxel in the treatment of cancer in asubject.

In some embodiments, the present disclosure pertains, at least in part,to use of Compound A with docetaxel in reducing or preventing toxicity,hypersensitivity-type infusion reactions, and other negative outcomesresulting from or associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject suffering from cancer.

In some embodiments, the present disclosure provides use of Compound Awith docetaxel in the treatment of cancer in a subject in need thereof,wherein the subject is administered docetaxel orally at an amount ofabout 15 mg/m² to about 450 mg/m² once a day and for 1-7 times a week;

wherein Compound A administered to the subject once a day and for 1-7times a week; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides use of Compound Awith docetaxel in reducing hematologic toxicity and/or neurotoxicity,and/or other toxicities or symptoms (e.g., skin toxicity, nausea,vomiting, diarrhea, fatigue, sensory neuropathy, and infection) in asubject suffering from cancer and undergoing docetaxel therapy, whereinthe subject is administered docetaxel orally at an amount of about 15mg/m² to about 450 mg/m2 once a day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day and for 1-7times a week; and

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week, and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the present disclosure provides the use of CompoundA with docetaxel in reducing or preventing hypersensitivity-typeinfusion reactions associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject in need thereof, wherein the subject is administered docetaxelorally at an amount of about 15 mg/m² to about 450 mg/m² once a day andfor 1-7 times a week;

wherein Compound A is administered to the subject once a day for 1-7times a week; and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the present disclosure pertains, at least in part,to Compound A for use in a combination therapy with docetaxel in thetreatment of cancer in a subject.

In some embodiments, the disclosure pertains, at least in part, toCompound A for use in a combination therapy with docetaxel in reducingor preventing toxicity, hypersensitivity-type infusion reactions, andother negative outcomes resulting from or associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject suffering from cancer.

In some embodiments, the present disclosure provides Compound A for usein a combination therapy with docetaxel in the treatment of cancer in asubject in need thereof, wherein Compound A is administered to thesubject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m2 to about 450 mg/m² once a day and for 1-7 times aweek; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides Compound A for usein a combination therapy with docetaxel for reducing hematologictoxicity and/or neurotoxicity, and/or other toxicities or symptoms(e.g., skin toxicity, nausea, vomiting, diarrhea, fatigue, sensoryneuropathy, and infection) in a subject suffering from cancer andundergoing docetaxel therapy, wherein Compound A is administered to thesubject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m2 to about 450 mg/m² once a day and for 1-7 times aweek;

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides Compound A for usein a combination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof, wherein thesubject is administered docetaxel orally at an amount of about 15 mg/m²to about 450 mg/m² once a day and for 1-7 times a week;

wherein Compound A is administered to the subject once a day for 1-7times a week; and wherein Compound A is administered simultaneously withor prior to the docetaxel.

In some embodiments, the disclosure pertains, at least in part, to amedicament comprising Compound A for use in a combination therapy withdocetaxel in the treatment of cancer in a subject.

In some embodiments, the present disclosure pertains, at least in part,to a medicament comprising Compound A for use in a combination therapywith docetaxel in reducing or preventing toxicity, hypersensitivity-typeinfusion reactions, and other negative outcomes resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer.

In some embodiments, the present disclosure provides a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of cancer in a subject in need thereof, wherein themedicament is administered to the subject once a day and for 1-7 times aweek;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek; and wherein the medicament is administered simultaneously with orprior to the docetaxel.

In some embodiments, the present disclosure provides a medicamentcomprising Compound A for use in a combination therapy with docetaxelfor reducing hematologic toxicity and/or neurotoxicity, and/or othertoxicities or symptoms (e.g., skin toxicity, nausea, vomiting, diarrhea,fatigue, sensory neuropathy, and infection) in a subject suffering fromcancer and undergoing docetaxel therapy, wherein the medicament isadministered to the subject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek;

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week; and

wherein the medicament is administered simultaneously with or prior tothe docetaxel.

In some embodiments, the present disclosure provides a medicamentcomprising Compound A in a combination therapy with docetaxel forreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject in needthereof, wherein the medicament is administered to the subject once aday for 1-7 times a week; and

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek;

wherein the medicament administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure pertains, at least in part,to use of Compound A in a combination therapy with docetaxel in thetreatment of cancer in a subject.

In some embodiments, the present disclosure pertains, at least in part,to use of Compound A in a combination therapy with docetaxel for use inreducing or preventing toxicity, hypersensitivity-type infusionreactions, and other negative outcomes resulting from or associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject suffering fromcancer.

In some embodiments, the present disclosure provides use of Compound Ain a combination therapy with docetaxel in the treatment of cancer in asubject in need thereof, wherein Compound A is administered to thesubject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides use of Compound Ain a combination therapy with docetaxel for reducing hematologictoxicity and/or neurotoxicity, and/or other toxicities or symptoms(e.g., skin toxicity, nausea, vomiting, diarrhea, fatigue, sensoryneuropathy, and infection) in a subject suffering from cancer andundergoing docetaxel therapy, wherein Compound A is administered to thesubject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek;

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides use of Compound Ain a combination therapy with docetaxel in reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject in need thereof, wherein Compound Ais administered to the subject once a day and for 1-7 times a week;

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek;

wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 toabout 24 hours once every three weeks, once every two weeks, or onceevery week; and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 1 hour once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 2 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 3 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 6 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 9 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 12 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 15 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 18 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 21 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 24 hours once every three weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused atabout 60 mg/m² to 100 mg/m² over a period of about 1 hour, about 2hours, about 3 hours, about 6 hours, about 9 hours, about 12 hours,about 15 hours, about 18 hours, about 21 hours, or about 24 hours onceevery three weeks. In some embodiments, the intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)is infused at about 75 mg/m².

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 1 hour once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 2 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 3 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 6 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 9 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 12 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 15 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 18 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 21 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 24 hours once every two weeks.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused atabout 30 mg/m² to 80 mg/m² over a period of about 1 hour, about 2 hours,about 3 hours, about 6 hours, about 9 hours, about 12 hours, about 15hours, about 18 hours, about 21 hours, or about 24 hours once every twoweeks. In some embodiments, the intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) is infusedat about 50 mg/m².

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 1 hour once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 2 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 3 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 6 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 9 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 12 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 15 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 18 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 21 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused over aperiod of about 24 hours once every week.

In some embodiments, the intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) is infused atabout 30 mg/m² to 60 mg/m² over a period of about 1 hour, about 2 hours,about 3 hours, about 6 hours, about 9 hours, about 12 hours, about 15hours, about 18 hours, about 21 hours, or about 24 hours once everyweek. In some embodiments, the intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) is infusedat about 30 mg/m². In some embodiments, the docetaxel is intravenouslyadministered for a period of five or six weeks.

In some embodiments, the hematologic toxicity associated with theintravenous administration of docetaxel in a subject suffering fromcancer includes anemia and/or myelosuppression. In some embodiments, themyelosuppression may be from leukopenia, neutropenia, and/orthrombocytopenia, or any combination thereof.

In some embodiments, the neurotoxicity associated with the intravenousadministration of docetaxel in a subject suffering from cancer includessymptoms such as numbness, tingling, sharp pain, jabbing pain, burningpain, extreme sensitivity, loss of coordination, falling, weakness,paralysis, sweating, heat intolerance, dizziness, changes in bloodpressure, bowel problems, and bladder problems, or any combinationthereof.

In some embodiments, the present disclosure provides a method forreducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer, comprising:

a. oral administration of docetaxel at an amount of about 15 mg/m² toabout 450 mg/m² to the subject once a day and for 1-7 times a week; and

b. oral administration of Compound A;

to the subject once a day and for 1-7 times a week, wherein the orallyadministered docetaxel reaches therapeutic blood or plasma levels in thesubject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides Compound A for usein reducing or preventing hypersensitivity-type infusion reactionsassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer, wherein the subject is administered docetaxel orally at anamount of about 15 mg/m² to about 450 mg/m² once a day and for 1-7 timesa week;

wherein Compound A:

is administered to the subject once a day and for 1-7 times a week; and

wherein the orally administered docetaxel reaches therapeutic blood orplasma levels in the subject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides the use of CompoundA in the manufacture of a medicament for use with docetaxel in reducingor preventing hypersensitivity-type infusion reactions associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject suffering fromcancer, wherein the subject is administered docetaxel orally at anamount of about 15 mg/m² to about 450 mg/m² once a day and for 1-7 timesa week;

wherein Compound A:

is administered to the subject once a day and for 1-7 times a week; and

wherein the orally administered docetaxel reaches therapeutic blood orplasma levels in the subject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides the use of CompoundA with docetaxel in reducing or preventing hypersensitivity-typeinfusion reactions associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject suffering from cancer, wherein the subject is administereddocetaxel orally at an amount of about 15 mg/m² to about 450 mg/m² oncea day and for 1-7 times a week;

wherein Compound A:

is administered to the subject once a day and for 1-7 times a week; and

wherein the orally administered docetaxel reaches therapeutic blood orplasma levels in the subject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides Compound A for usein a combination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject suffering from cancer, whereinCompound A:

is administered to the subject once a day and for 1-7 times a week; and

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek; and wherein the orally administered docetaxel reaches therapeuticblood or plasma levels in the subject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the present disclosure provides a medicament foruse in a combination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject suffering from cancer, wherein themedicament comprises Compound A:

which is administered to the subject once a day and for 1-7 times aweek; and

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek; and wherein the orally administered docetaxel reaches therapeuticblood or plasma levels in the subject, and wherein the medicament isadministered simultaneously with or prior to the docetaxel.

In some embodiments, the present disclosure provides use of Compound Ain a combination therapy with docetaxel for reducing or preventinghypersensitivity-type infusion reactions associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject suffering from cancer, whereinCompound A:

is administered to the subject once a day and for 1-7 times a week; and

wherein the subject is also administered docetaxel orally at an amountof about 15 mg/m² to about 450 mg/m² once a day and for 1-7 times aweek; and wherein the orally administered docetaxel reaches therapeuticblood or plasma levels in the subject, and

wherein Compound A is administered simultaneously with or prior to thedocetaxel.

In some embodiments, the hypersensitivity-type infusion reactionsassociated with the intravenous administration of docetaxel in a subjectsuffering from cancer includes any sign or symptom on the first day ofintravenous administration of docetaxel. In some embodiments, the signsor symptoms in the subject include fever, rash, hives, pruritus,flushing, swelling, dyspnea, bronchospasm, stridor, reduced pulmonaryexpiratory flow, hypoxia, hypertension, hypotension, hypotonia, syncope,falling, incontinence, abdominal pain, vomiting, urticaria, facialswelling, eye disorders, headache, arrhythmia, tachycardia, nausea,chest pain, and anaphylaxis, and/or any combination thereof.

In some embodiments, the docetaxel is administered orally.

In some embodiments, the docetaxel is administered at an amount of about15 mg/m² to about 450 mg/m².

In some embodiments, the docetaxel is administered at an amount of about15 mg/m² to about 400 mg/m².

In some embodiments, the docetaxel is administered at an amount of about20 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about25 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about30 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about35 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about40 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about45 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m² to about 150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m² to about 225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about200 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about225 mg/m² to about 300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about250 mg/m² to about 350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about15 mg/m².

In some embodiments, the docetaxel is administered at an amount of about20 mg/m².

In some embodiments, the docetaxel is administered at an amount of about25 mg/m².

In some embodiments, the docetaxel is administered at an amount of about30 mg/m².

In some embodiments, the docetaxel is administered at an amount of about35 mg/m².

In some embodiments, the docetaxel is administered at an amount of about40 mg/m².

In some embodiments, the docetaxel is administered at an amount of about45 mg/m².

In some embodiments, the docetaxel is administered at an amount of about50 mg/m².

In some embodiments, the docetaxel is administered at an amount of about55 mg/m².

In some embodiments, the docetaxel is administered at an amount of about60 mg/m².

In some embodiments, the docetaxel is administered at an amount of about65 mg/m².

In some embodiments, the docetaxel is administered at an amount of about70 mg/m².

In some embodiments, the docetaxel is administered at an amount of about75 mg/m².

In some embodiments, the docetaxel is administered at an amount of about80 mg/m².

In some embodiments, the docetaxel is administered at an amount of about85 mg/m².

In some embodiments, the docetaxel is administered at an amount of about90 mg/m².

In some embodiments, the docetaxel is administered at an amount of about95 mg/m².

In some embodiments, the docetaxel is administered at an amount of about100 mg/m².

In some embodiments, the docetaxel is administered at an amount of about105 mg/m².

In some embodiments, the docetaxel is administered at an amount of about110 mg/m².

In some embodiments, the docetaxel is administered at an amount of about115 mg/m².

In some embodiments, the docetaxel is administered at an amount of about120 mg/m².

In some embodiments, the docetaxel is administered at an amount of about125 mg/m².

In some embodiments, the docetaxel is administered at an amount of about130 mg/m².

In some embodiments, the docetaxel is administered at an amount of about135 mg/m².

In some embodiments, the docetaxel is administered at an amount of about140 mg/m².

In some embodiments, the docetaxel is administered at an amount of about145 mg/m².

In some embodiments, the docetaxel is administered at an amount of about150 mg/m².

In some embodiments, the docetaxel is administered at an amount of about155 mg/m².

In some embodiments, the docetaxel is administered at an amount of about160 mg/m².

In some embodiments, the docetaxel is administered at an amount of about165 mg/m².

In some embodiments, the docetaxel is administered at an amount of about170 mg/m².

In some embodiments, the docetaxel is administered at an amount of about175 mg/m².

In some embodiments, the docetaxel is administered at an amount of about180 mg/m².

In some embodiments, the docetaxel is administered at an amount of about185 mg/m².

In some embodiments, the docetaxel is administered at an amount of about190 mg/m².

In some embodiments, the docetaxel is administered at an amount of about195 mg/m².

In some embodiments, the docetaxel is administered at an amount of about200 mg/m².

In some embodiments, the docetaxel is administered at an amount of about205 mg/m².

In some embodiments, the docetaxel is administered at an amount of about210 mg/m².

In some embodiments, the docetaxel is administered at an amount of about215 mg/m².

In some embodiments, the docetaxel is administered at an amount of about220 mg/m².

In some embodiments, the docetaxel is administered at an amount of about225 mg/m².

In some embodiments, the docetaxel is administered at an amount of about230 mg/m².

In some embodiments, the docetaxel is administered at an amount of about235 mg/m².

In some embodiments, the docetaxel is administered at an amount of about240 mg/m².

In some embodiments, the docetaxel is administered at an amount of about245 mg/m².

In some embodiments, the docetaxel is administered at an amount of about250 mg/m².

In some embodiments, the docetaxel is administered at an amount of about275 mg/m².

In some embodiments, the docetaxel is administered at an amount of about300 mg/m².

In some embodiments, the docetaxel is administered at an amount of about325 mg/m².

In some embodiments, the docetaxel is administered at an amount of about350 mg/m².

In some embodiments, the docetaxel is administered at an amount of about375 mg/m².

In some embodiments, the docetaxel is administered at an amount of about400 mg/m².

In some embodiments, the docetaxel is administered at an amount of about425 mg/m².

In some embodiments, the docetaxel is administered at an amount of about450 mg/m².

In some embodiments, the docetaxel is administered as a single dose on asingle day.

In some embodiments, the docetaxel is administered on consecutive days.

In some embodiments, the docetaxel is administered 1-7 times per week.

In some embodiments, the docetaxel is administered 1-6 times per week.In some embodiments, the docetaxel is administered 1-5 times per week.In some embodiments, the docetaxel is administered 1-4 times per week.In some embodiments, the docetaxel is administered 1-3 times per week.In some embodiments, the docetaxel is administered 1-2 times per week.

In some embodiments, the docetaxel is administered 2-7 times per week.In some embodiments, the docetaxel is administered 2-6 times per week.In some embodiments, the docetaxel is administered 2-5 times per week.In some embodiments, the docetaxel is administered 2-4 times per week.In some embodiments, the docetaxel is administered 2-3 times per week.

In some embodiments, the docetaxel is administered 3-6 times per week.In some embodiments, the docetaxel is administered 3-5 times per week.In some embodiments, the docetaxel is administered 3-4 times per week.

In some embodiments, the docetaxel is administered 4-6 times per week.In some embodiments, the docetaxel is administered 4-5 times per week.

In some embodiments, the docetaxel is administered 5-6 times per week.In some embodiments, the docetaxel is administered less than five timesper week.

In some embodiments, the docetaxel is administered once per week. Insome embodiments, the docetaxel is administered twice per week. In someembodiments, the docetaxel is administered three times per week. In someembodiments, the docetaxel is administered four times per week. In someembodiments, the docetaxel is administered five times per week. In someembodiments, the docetaxel is administered six times per week.

In some embodiments, the docetaxel is administered at a single dosetwice per week. In some embodiments, the docetaxel is administered at asingle dose three times per week. In some embodiments, the docetaxel isadministered at a single dose four times per week. In some embodiments,the docetaxel is administered at a single dose five times per week. Insome embodiments, the docetaxel is administered at a single dose sixtimes per week.

In some embodiments, the docetaxel is administered at least once perweek. In some embodiments, the docetaxel is administered at least onceper week at an amount of any dosage described above. In someembodiments, the docetaxel is administered once over a three-weekperiod. In some embodiments, the docetaxel is administered as one singledose over a three-week period.

In some embodiments, the docetaxel is administered at least once perweek at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least once per weekat an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m², about120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m², about 140mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least once perweek at an amount of about 150 mg/m², about 155 mg/m², about 160 mg/m²,about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180 mg/m²,about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200 mg/m²,about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220 mg/m²,about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240 mg/m²,about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260 mg/m²,about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280 mg/m²,about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300 mg/m²,about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320 mg/m²,about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340 mg/m²,about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360 mg/m²,about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380 mg/m²,about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400 mg/m².In some embodiments, the docetaxel is administered at least once perweek at an amount of about 150 mg/m², about 155 mg/m², about 160 mg/m²,about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180 mg/m²,about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200 mg/m²,about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220 mg/m²,about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240 mg/m²,about 245 mg/m², or about 250 mg/m². In some embodiments, the docetaxelis administered at least once per week at an amount of about 225 mg/m²,about 250 mg/m², about 275 mg/m², about 300 mg/m², about 325 mg/m², orabout 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,once over a three-week period. In some embodiments, the docetaxel isadministered at a single dose at about 225 mg/m², once over a three-weekperiod. In some embodiments, the docetaxel is administered at about 150mg/m², once over a three-week period. In some embodiments, the docetaxelis administered at a single dose at about 150 mg/m², once over athree-week period. In some embodiments, the docetaxel is administered atabout 75 mg/m², once over a three-week period. In some embodiments, thedocetaxel is administered at a single dose at about 75 mg/m², once overa three-week period.

In some embodiments, the docetaxel is administered at least twice perweek. In some embodiments, the docetaxel is administered at least twiceper week at an amount of any dosage as described above. In someembodiments, the docetaxel is administered twice over a three-weekperiod. In some embodiments, the docetaxel is administered twice onconsecutive days over a three-week period. In some embodiments, thedocetaxel is administered as two single doses over a three-week period.

In some embodiments, the docetaxel is administered at least twice perweek at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least twice per weekat an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m², about120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m², about 140mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least twice perweek at an amount of about 150 mg/m², about 155 mg/m², about 160 mg/m²,about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180 mg/m²,about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200 mg/m²,about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220 mg/m²,about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240 mg/m²,about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260 mg/m²,about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280 mg/m²,about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300 mg/m²,about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320 mg/m²,about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340 mg/m²,about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360 mg/m²,about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380 mg/m²,about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400 mg/m².In some embodiments, the docetaxel is administered at least twice perweek at an amount of about 150 mg/m², about 155 mg/m², about 160 mg/m²,about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180 mg/m²,about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200 mg/m²,about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220 mg/m²,about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240 mg/m²,about 245 mg/m², or about 250 mg/m². In some embodiments, the docetaxelis administered at least twice per week at an amount of about 225 mg/m²,about 250 mg/m², about 275 mg/m², about 300 mg/m², about 325 mg/m², orabout 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,twice on consecutive days over a three-week period. In some embodiments,the docetaxel is administered as a single dose at about 225 mg/m², twiceon consecutive days over a three-week period. In some embodiments, thedocetaxel is administered at about 150 mg/m², twice on consecutive daysover a three-week period. In some embodiments, the docetaxel isadministered as single doses at about 150 mg/m², twice on consecutivedays over a three-week period. In some embodiments, the docetaxel isadministered at about 75 mg/m², twice on consecutive days over athree-week period. In some embodiments, the docetaxel is administered assingle doses at about 75 mg/m², twice on consecutive days over athree-week period.

In some embodiments, the docetaxel is administered at least three timesper week. In some embodiments, the docetaxel is administered onconsecutive days. In some embodiments, the docetaxel is administered atleast three times per week at an amount of any dosage as describedabove. In some embodiments, the docetaxel is administered three timesover a three-week period. In some embodiments, the docetaxel isadministered three times on consecutive days over a three-week period.In some embodiments, the docetaxel is administered as three single dosesover a three-week period.

In some embodiments, the docetaxel is administered at least three timesper week at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least three times perweek at an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m²,about 120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m²,about 140 mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least three timesper week at an amount of about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260mg/m², about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280mg/m², about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300mg/m², about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320mg/m², about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340mg/m², about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360mg/m², about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380mg/m², about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400mg/m². In some embodiments, the docetaxel is administered at least threetimes per week at an amount of about 150 mg/m², about 155 mg/m², about160 mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², or about 250 mg/m². In some embodiments, thedocetaxel is administered at least three times per week at an amount ofabout 225 mg/m², about 250 mg/m², about 275 mg/m², about 300 mg/m²,about 325 mg/m², or about 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,three times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as single doses at about 225mg/m², three times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered at about 150 mg/m², threetimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered as single doses at about 150 mg/m², threetimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered at about 75 mg/m², three times onconsecutive days over a three-week period. In some embodiments, thedocetaxel is administered as single doses at about 75 mg/m², three timeson consecutive days over a three-week period.

In some embodiments, the docetaxel is administered at least four timesper week. In some embodiments, the docetaxel is administered onconsecutive days. In some embodiments, the docetaxel is administered atleast four times per week at an amount of any dosage as described above.In some embodiments, the docetaxel is administered four times over athree-week period. In some embodiments, the docetaxel is administeredfour times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as four single doses over athree-week period.

In some embodiments, the docetaxel is administered at least four timesper week at an amount of about 25 mg/m2, about 30 mg/m2, about 35 mg/m2,about 40 mg/m2, about 45 mg/m2, about 50 mg/m2, about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least four times perweek at an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m²,about 120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m²,about 140 mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least four timesper week at an amount of about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260mg/m², about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280mg/m², about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300mg/m², about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320mg/m², about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340mg/m², about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360mg/m², about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380mg/m², about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400mg/m². In some embodiments, the docetaxel is administered at least fourtimes per week at an amount of about 125 mg/m², about 130 mg/m², about135 mg/m², about 140 mg/m², about 145 mg/m², about 150 mg/m², about 155mg/m², about 160 mg/m², about 165 mg/m², about 170 mg/m², about 175mg/m², about 180 mg/m², about 185 mg/m², about 190 mg/m², about 195mg/m², about 200 mg/m², about 205 mg/m², about 210 mg/m², about 215mg/m², about 220 mg/m², about 225 mg/m², about 230 mg/m², about 235mg/m², about 240 mg/m², about 245 mg/m², or about 250 mg/m². In someembodiments, the docetaxel is administered at least four times per weekat an amount of about 125 mg/m², about 130 mg/m², about 135 mg/m², about140 mg/m², about 145 mg/m², about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 200mg/m², about 225 mg/m², or about 250 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,four times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as single doses at about 225mg/m², four times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered at about 150 mg/m², fourtimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered as single doses at about 150 mg/m², fourtimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered at about 75 mg/m², four times onconsecutive days over a three-week period. In some embodiments, thedocetaxel is administered as single doses at about 75 mg/m², four timeson consecutive days over a three-week period.

In some embodiments, the docetaxel is administered at least five timesper week. In some embodiments, the docetaxel is administered onconsecutive days. In some embodiments, the docetaxel is administered atleast five times per week at an amount of any dosage as described above.In some embodiments, the docetaxel is administered five times over athree-week period. In some embodiments, the docetaxel is administeredfive times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as five single doses over athree-week period.

In some embodiments, the docetaxel is administered at least five timesper week at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least 5 times perweek at an amount of about 110 mg/m², about 120 mg/m², about 130 mg/m²,about 140 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least five timesper week at an amount of about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260mg/m², about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280mg/m², about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300mg/m², about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320mg/m², about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340mg/m², about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360mg/m², about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380mg/m², about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400mg/m². In some embodiments, the docetaxel is administered at least fivetimes per week at an amount of about 250 mg/m², about 275 mg/m², about300 mg/m², about 325 mg/m², or about 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,five times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as single doses at about 225mg/m², five times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered at about 150 mg/m², fivetimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered as single doses at about 150 mg/m², fivetimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered at about 75 mg/m², five times onconsecutive days over a three-week period. In some embodiments, thedocetaxel is administered as single doses at about 75 mg/m², five timeson consecutive days over a three-week period.

In some embodiments, the docetaxel is administered at least six timesper week. In some embodiments, the docetaxel is administered onconsecutive days. In some embodiments, the docetaxel is administered atleast six times per week at an amount of any dosage as described above.In some embodiments, the docetaxel is administered six times over athree-week period. In some embodiments, the docetaxel is administeredsix times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as six single doses over athree-week period.

In some embodiments, the docetaxel is administered at least six timesper week at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least six times perweek at an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m²,about 120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m²,about 140 mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least six timesper week at an amount of about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260mg/m², about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280mg/m², about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300mg/m², about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320mg/m², about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340mg/m², about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360mg/m², about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380mg/m², about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400mg/m². In some embodiments, the docetaxel is administered at least sixtimes per week at an amount of about 250 mg/m², about 275 mg/m², about300 mg/m², about 325 mg/m², or about 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,six times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as single doses at about 225mg/m², six times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered at about 150 mg/m², six timeson consecutive days over a three-week period. In some embodiments, thedocetaxel is administered as single doses at about 150 mg/m², six timeson consecutive days over a three-week period. In some embodiments, thedocetaxel is administered at about 75 mg/m², six times on consecutivedays over a three-week period. In some embodiments, the docetaxel isadministered as single doses at about 75 mg/m², six times on consecutivedays over a three-week period.

In some embodiments, the docetaxel is administered at least seven timesper week. In some embodiments, the docetaxel is administered onconsecutive days. In some embodiments, the docetaxel is administered atleast seven times per week at an amount of any dosage as describedabove. In some embodiments, the docetaxel is administered seven timesover a three-week period. In some embodiments, the docetaxel isadministered seven times on consecutive days over a three-week period.In some embodiments, the docetaxel is administered as seven single dosesover a three-week period.

In some embodiments, the docetaxel is administered at least seven timesper week at an amount of about 25 mg/m², about 30 mg/m², about 35 mg/m²,about 40 mg/m², about 45 mg/m², about 50 mg/m², about 55 mg/m², about 60mg/m², about 65 mg/m², about 70 mg/m², about 75 mg/m², about 80 mg/m²,about 85 mg/m², about 90 mg/m², about 95 mg/m², or about 100 mg/m². Insome embodiments, the docetaxel is administered at least seven times perweek at an amount of about 105 mg/m², about 110 mg/m², about 115 mg/m²,about 120 mg/m², about 125 mg/m², about 130 mg/m², about 135 mg/m²,about 140 mg/m², about 145 mg/m², or about 150 mg/m².

In some embodiments, the docetaxel is administered at least seven timesper week at an amount of about 150 mg/m², about 155 mg/m², about 160mg/m², about 165 mg/m², about 170 mg/m², about 175 mg/m², about 180mg/m², about 185 mg/m², about 190 mg/m², about 195 mg/m², about 200mg/m², about 205 mg/m², about 210 mg/m², about 215 mg/m², about 220mg/m², about 225 mg/m², about 230 mg/m², about 235 mg/m², about 240mg/m², about 245 mg/m², about 250 mg/m², about 255 mg/m², about 260mg/m², about 265 mg/m², about 270 mg/m², about 275 mg/m², about 280mg/m², about 285 mg/m², about 290 mg/m², about 295 mg/m², about 300mg/m², about 305 mg/m², about 310 mg/m², about 315 mg/m², about 320mg/m², about 325 mg/m², about 330 mg/m², about 335 mg/m², about 340mg/m², about 345 mg/m², about 350 mg/m², about 355 mg/m², about 360mg/m², about 365 mg/m², about 370 mg/m², about 375 mg/m², about 380mg/m², about 385 mg/m², about 390 mg/m², about 395 mg/m², or about 400mg/m². In some embodiments, the docetaxel is administered at least seventimes per week at an amount of about 250 mg/m², about 275 mg/m², about300 mg/m², about 325 mg/m², or about 350 mg/m².

In some embodiments, the docetaxel is administered at about 225 mg/m²,seven times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered as single doses at about 225mg/m², seven times on consecutive days over a three-week period. In someembodiments, the docetaxel is administered at about 150 mg/m², seventimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered as single doses at about 150 mg/m², seventimes on consecutive days over a three-week period. In some embodiments,the docetaxel is administered at about 75 mg/m², seven times onconsecutive days over a three-week period. In some embodiments, thedocetaxel is administered as single doses at about 75 mg/m², seven timeson consecutive days over a three-week period.

In some embodiments, oral administration of docetaxel (i.e.,administration of an oral formulation of docetaxel) is preceded by IVadministration of docetaxel. In some embodiments, the docetaxel isadministered intravenously according to the dosage amount and dosageregimen described herein, followed by administration of an oralformulation of docetaxel as described herein. In some embodiments, thedocetaxel is administered intravenously according to the dosage amountonce on the first day of the first week, and the administration of anoral formulation of docetaxel starts on the first day of the fourthweek, according to the dosage amount and dosage regimen describedherein.

In some embodiments, oral administration of docetaxel (i.e.,administration of an oral formulation of docetaxel) is preceded by apremedication regimen. In some embodiments, the premedication comprisesan antiemetic (e.g., dexamethasone), an oral corticosteroid, or ananti-histamine. In some embodiments, the premedication comprises anantiemetic. In some embodiments, the premedication comprisesdexamethasone. In some embodiments, the premedication comprises an oralcorticosteroid. In some embodiments, the premedication comprises ananti-histamine.

In some embodiments, the present disclosure includes examples whereinCompound A is administered orally.

In some embodiments, Compound A is administered at an amount of about 1mg to about 500 mg.

In some embodiments, Compound A is administered at about 1 mg to 400 mg.

In some embodiments, Compound A is administered at about 1 mg to 300 mg.

In some embodiments, Compound A is administered at about 5 mg to 200 mg.

In some embodiments, Compound A is administered at about 10 mg to 100mg.

In some embodiments, Compound A is administered at about 15 mg to 50 mg.

In some embodiments, Compound A is administered at about 5 mg.

In some embodiments, Compound A is administered at about 10 mg.

In some embodiments, Compound A is administered at about 15 mg.

In some embodiments, Compound A is administered at about 20 mg.

In some embodiments, Compound A is administered at about 25 mg.

In some embodiments, Compound A is administered at about 30 mg.

In some embodiments, Compound A is administered at about 35 mg.

In some embodiments, Compound A is administered at about 45 mg.

In some embodiments, Compound A is administered at about 50 mg.

In some embodiments, Compound A and the docetaxel are administered onthe same day.

In some embodiments, Compound A and the docetaxel are administered onthe same day as a single dose.

In some embodiments, Compound A and the docetaxel are administered onthe same day as a single dose once a week.

In some embodiments, Compound A and the docetaxel are administered onthe same day as a single dose once every three weeks.

In some embodiments, Compound A and the docetaxel are administered onthe same day as two single daily doses.

In some embodiments, Compound A and the docetaxel are administered onthe same day as two single daily doses once a week.

In some embodiments, Compound A and the docetaxel are administered onthe same day as two single daily doses once every three weeks.

In some embodiments, Compound A is administered simultaneously withdocetaxel.

In some embodiments, Compound A is administered before the docetaxel isadministered.

In some embodiments, Compound A is administered about 5 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 10 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 15 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 30 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 45 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 60 minutes beforethe docetaxel is administered.

In some embodiments, Compound A is administered about 2 hours before thedocetaxel is administered.

In some embodiments, Compound A is administered about 3 hours before thedocetaxel is administered.

In some embodiments, Compound A is administered about 4 hours before thedocetaxel is administered.

In some embodiments, Compound A is administered about 6 hours before thedocetaxel is administered.

In some embodiments, Compound A is administered about 8 hours before thedocetaxel is administered.

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1-24 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 1-24 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 1-24 hours once every week, as measured by AUC(0-00).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1-20 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 1-20 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 1-20 hours once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1-16 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 1-16 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 1-16 hours once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 2-12 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 2-12 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 2-12 hours once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 2-10 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 2-10 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 2-10 hours once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 3-8 hours once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 3-8 hours once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 3-8 hours once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 60 minutes once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 60 minutes once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over aperiod of about 60 minutes once every week, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 70-90 mg/m² over a period of about 60 minutes onceevery three weeks, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 75-85 mg/m² over a period of about 60 minutes onceevery three weeks, as measured by AUC_((0→∞)).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 80 mg/m² over a period of about 60 minutes onceevery three weeks, as measured by AUC(0→∞).

In some embodiments of the present disclosure, the plasma exposure ofthe orally administered docetaxel, as measured by AUC(0→∞), is equal toor greater than the plasma exposure of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 75 mg/m² over a period of about 60 minutes onceevery three weeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to the AUC(0→∞) of intravenously administered docetaxel e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m² (e.g., 75 mg/m²) over a period of about 60 minutesonce every three weeks, or at an amount of about 30-100 mg/m² (e.g., 50mg/m²) over a period of about 60 minutes once every two weeks, or at anamount of about 30-75 mg/m² (e.g., 30 mg/m²) over a period of about 60minutes once every week, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to the AUC(0→∞) of intravenously administered docetaxel e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 70-90 mg/m² over a period of about 60 minutes once every threeweeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to the AUC(0→∞) of intravenously administered docetaxel e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 75-85 mg/m² over a period of about 60 minutes once every threeweeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to the AUC(0→∞) of intravenously administered docetaxel e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 80 mg/m² over a period of about 60 minutes once every three weeks,as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to the AUC(0→∞) of intravenously administered docetaxel e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 75 mg/m² over a period of about 60 minutes once every three weeks,as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis greater than the AUC(0→∞) of intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) at anamount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period of about 60minutes once every three weeks, or at an amount of about 30-100 mg/m²(e.g., 50 mg/m²) over a period of about 60 minutes once every two weeks,or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) over a period ofabout 60 minutes once every week, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis greater than the AUC(0→∞) of intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) at anamount of about 70-90 mg/m² over a period of about 60 minutes once everythree weeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis greater than the AUC(0→∞) of intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) at anamount of about 75-85 mg/m² over a period of about 60 minutes once everythree weeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis greater than the AUC(0→∞) of intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) at anamount of about 80 mg/m² over a period of about 60 minutes once everythree weeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis greater than the AUC(0→∞) of intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) at anamount of about 75 mg/m² over a period of about 60 minutes once everythree weeks, as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85,90, 95, or 100% greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 60minutes once every three weeks, or at an amount of about 30-100 mg/m²(e.g., 50 mg/m²) over a period of about 60 minutes once every two weeks,or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²), as measured byAUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 10% greater (e.g., at least 10% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 20% greater (e.g., at least 20% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 30% greater (e.g., at least 30% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 40% greater (e.g., at least 40% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 50% greater (e.g., at least 50% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 60% greater (e.g., at least 60% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 70% greater (e.g., at least 70% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 80% greater (e.g., at least 80% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 90% greater (e.g., at least 90% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis at least about 100% greater (e.g., at least 100% greater) than theAUC(0→∞) of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 100% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of 60-100 mg/m², about70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over aperiod of about 60 minutes once every three weeks, or at an amount ofabout 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60 minutesonce every two weeks, or at an amount of about 30-75 mg/m² (e.g., 30mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 90% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 80% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 70% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 60% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 50% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 40% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 35% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 30% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 25% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10% greater to about 20% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 15% greater to about 25% greater than the AUC(0→∞) ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 60 minutes once every three weeks, or at anamount of about 30-100 mg/m² (e.g., 50 mg/m²) over a period of about 60minutes once every two weeks, or at an amount of about 30-75 mg/m²(e.g., 30 mg/m²), as measured by AUC(0→∞).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 500 ng·h/mL to about 15,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 1,000 ng·h/mL to about 15,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 1,500 ng·h/mL to about 10,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 2,000 ng·h/mL to about 10,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 2,000 ng·h/mL to about 9,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 3,000 ng·h/mL to about 9,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 3,000 ng·h/mL to about 8,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 3,000 ng-h/mL to about 7,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 4,000 ng·h/mL to about 7,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 5,000 ng·h/mL to about 7,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 2,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 3,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 4,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 5,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 6,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 7,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 8,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 9,000 ng·h/mL.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis about 10,000 ng·h/mL.

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 15 mg/m² to about 3,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 25 mg/m² to about 2,500 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 50 mg/m² to about 2,500 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 75 mg/m² to about 2,500 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 100 mg/m² to about 2,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 150 mg/m² to about 2,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 200 mg/m² to about 2,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 250 mg/m² to about 2,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 2,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,900 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,800 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,700 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,600 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,500 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,400 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,300 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,200 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,100 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 1,000 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 300 mg/m² to about 900 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 350 mg/m² to about 850 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 400 mg/m² to about 800 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 450 mg/m² to about 750 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 500 mg/m² to about 700 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 550 mg/m² to about 650 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is about 15, 25, 50, 75, 100, 150, 200, 250, 300,325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 605, 610,615, 620, 625, 630, 635, 640, 645, 650, 655, 660, 665, 670, 675, 680,685, 690, 695, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950,975, 1,000, 1,025, 1,050, 1,075, 1,100, 1,125, 1,150, 1,175, 1,200,1,225, 1,250, 1,275, 1,300, 1,325, 1,350, 1,375, 1,400, 1,425, 1,450,1,475, 1,500, 1,525, 1,550, 1,575, 1,600, 1,625, 1,650, 1,675, 1,700,1,725, 1,750, 1,775, or 1,800 mg/m².

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 25 mg/m² (e.g., at least 25mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 50 mg/m² (e.g., at least 50mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 75 mg/m² (e.g., at least 75mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 100 mg/m² (e.g., at least 100mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 125 mg/m² (e.g., at least 125mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 150 mg/m² (e.g., at least 150mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 175 mg/m² (e.g., at least 175mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 200 mg/m² (e.g., at least 200mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 225 mg/m² (e.g., at least 225mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 250 mg/m² (e.g., at least 250mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 275 mg/m² (e.g., at least 275mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 300 mg/m² (e.g., at least 300mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 325 mg/m² (e.g., at least 325mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 350 mg/m² (e.g., at least 350mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 375 mg/m² (e.g., at least 375mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 400 mg/m² (e.g., at least 400mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 425 mg/m² (e.g., at least 425mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 450 mg/m² (e.g., at least 450mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 475 mg/m² (e.g., at least 475mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 500 mg/m² (e.g., at least 500mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 525 mg/m² (e.g., at least 525mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 550 mg/m² (e.g., at least 550mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 575 mg/m² (e.g., at least 575mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 600 mg/m² (e.g., at least 600mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 615 mg/m² (e.g., at least 615mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 625 mg/m² (e.g., at least 625mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 630 mg/m² (e.g., at least 630mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 645 mg/m² (e.g., at least 645mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 650 mg/m² (e.g., at least 650mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 660 mg/m² (e.g., at least 660mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 675 mg/m² (e.g., at least 675mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 700 mg/m² (e.g., at least 700mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 725 mg/m² (e.g., at least 725mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 750 mg/m² (e.g., at least 750mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 775 mg/m² (e.g., at least 775mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 800 mg/m² (e.g., at least 800mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 825 mg/m² (e.g., at least 825mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 850 mg/m² (e.g., at least 850mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 875 mg/m² (e.g., at least 875mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 900 mg/m² (e.g., at least 900mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 975 mg/m² (e.g., at least 975mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,000 mg/m² (e.g., at least1,000 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,050 mg/m² (e.g., at least1,050 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,100 mg/m² (e.g., at least1,100 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,125 mg/m² (e.g., at least1,125 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,200 mg/m² (e.g., at least1,200 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,250 mg/m² (e.g., at least1,250 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,300 mg/m² (e.g., at least1,300 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,350 mg/m² (e.g., at least1,350 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,375 mg/m² (e.g., at least1,375 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,400 mg/m² (e.g., at least1,400 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,500 mg/m² (e.g., at least1,500 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,625 mg/m² (e.g., at least1,625 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,650 mg/m² (e.g., at least1,650 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,750 mg/m² (e.g., at least1,750 mg/m²).

In some embodiments, the total amount of the docetaxel orallyadministered per week is at least about 1,800 mg/m² (e.g., at least1,800 mg/m²).

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to or greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 60 minutes once every three weeks, or at an amount of about 30-100mg/m² (e.g., 50 mg/m²) over a period of about 60 minutes once every twoweeks, or at an amount of about 30-75 mg/m² (e.g., 30 mg/m²) in treatingcancer.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to or greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 70-90 mg/m² over a period of about 60 minutes onceevery three weeks in treating cancer.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to or greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 75-85 mg/m² over a period of about 60 minutes onceevery three weeks in treating cancer.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to or greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 80 mg/m² over a period of about 60 minutes onceevery three weeks in treating cancer.

In some embodiments, the AUC(0→∞) of the orally administered docetaxelis equal to or greater than the AUC(0→∞) of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 75 mg/m² over a period of about 60 minutes onceevery three weeks in treating cancer.

In some embodiments, the disclosure provides methods of treating cancerin a subject, and/or to methods for reducing or preventing toxicity,hypersensitivity-type infusion reactions and other negative outcomesresulting from or associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject suffering from cancer.

In some embodiments, the present disclosure provides Compound A for usein the treatment of cancer in a subject, and/or to Compound A for use inthe reducing or preventing toxicity, hypersensitivity-type infusionreactions and other negative outcomes resulting from or associated withintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) therapy in a subject suffering fromcancer.

In some embodiments, the present disclosure provides use of Compound Ain the manufacture of a medicament for use with docetaxel in thetreatment of cancer in a subject, and/or to use of Compound A in themanufacture of a medicament for use with docetaxel in reducing orpreventing toxicity, hypersensitivity-type infusion reactions and othernegative outcomes resulting from or associated with intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) therapy in a subject suffering from cancer.

In some embodiments, the present disclosure provides use of Compound Awith docetaxel for the treatment of cancer in a subject, and/or to useof Compound A with docetaxel for reducing or preventing toxicity,hypersensitivity-type infusion reactions and other negative outcomesresulting from or associated with intravenously administered docetaxel(e.g., Taxotere® or docetaxel formulated with polysorbate 80) therapy ina subject suffering from cancer.

In some embodiments, the present disclosure provides use of Compound Ain a combination therapy with docetaxel for treatment of cancer in asubject, and/or to use of Compound A in a combination therapy withdocetaxel for reducing or preventing toxicity, hypersensitivity-typeinfusion reactions and other negative outcomes resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer.

In some embodiments, the present disclosure provides use of a medicamentin a combination therapy with docetaxel for the treatment of cancer in asubject, and/or use of a medicament in a combination therapy withdocetaxel for the reducing or preventing toxicity, hypersensitivity-typeinfusion reactions and other negative outcomes resulting from orassociated with intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) therapy in a subject sufferingfrom cancer, wherein the medicament comprises Compound A.

In some embodiments, the intravenously administered docetaxel isformulated in compositions that comprise docetaxel and a pharmaceuticalexcipient or carrier that facilitates the intravenous administration ofdocetaxel. In some embodiments, the intravenously administered docetaxelis formulated with polysorbate 80, e.g., Tween 80®. In some embodiments,the intravenously administered docetaxel is Taxol®, or a generic versionthereof. In some embodiments, the intravenously administered docetaxelis formulated with a protein carrier. In some embodiments, theintravenously administered docetaxel is formulated in a compositioncomprising protein-bound docetaxel, (i.e., nab-docetaxel or ABI-008).

In some embodiments, the cancer is a disease that involves abnormal cellgrowth with the potential to invade or spread to other parts of thebody.

In some embodiments, the cancer is a malignant tumor or neoplasm.

In some embodiments, the cancer is breast cancer, pancreatic cancer,non-small cell lung cancer, ovarian cancer, AIDS-related Kaposi sarcoma,soft tissue sarcoma, esophageal cancer, melanoma, lymphoma, uterinecancer, peritoneal cancer, fallopian tube cancer, endometrial cancer,cervical cancer, thyroid cancer, gastric cancer, gastroesophagealjunction cancer, urothelial cancer, bladder cancer, oropharynx cancer,hypopharynx cancer, larynx cancer, head and neck cancer, germ cellcancer/tumors, prostate cancer, colon cancer, rectal cancer, kidneycancer, squamous cell carcinoma, leukemia, or non-Hodgkin lymphoma.

In some embodiments, the cancer is breast cancer, pancreatic cancer,non-small cell lung cancer, ovarian cancer, AIDS-related Kaposi sarcoma,esophageal cancer, melanoma, lymphoma, uterine cancer, peritonealcancer, fallopian tube cancer, endometrial cancer, cervical cancer,thyroid cancer, gastric cancer, gastroesophageal junction cancer,urothelial cancer, bladder cancer, oropharynx cancer, hypopharynxcancer, larynx cancer, head and neck cancer, or germ cell cancer/tumors.

In some embodiments, the cancer is breast cancer, non-small cell lungcancer, ovarian cancer, AIDS-related Kaposi sarcoma, esophageal cancer,bladder cancer, prostate cancer, or melanoma.

In some embodiments, the cancer is breast cancer, non-small cell lungcancer, ovarian cancer, or AIDS-related Kaposi sarcoma.

In some embodiments, the cancer is breast cancer. In some embodiments,the breast cancer is metastatic breast cancer. In some embodiments, thebreast cancer is carcinoma of the breast.

In some embodiments, the cancer is lung cancer. In some embodiments, thelung cancer is non-small cell lung cancer.

In some embodiments, the cancer is prostate cancer. In some embodiments,the prostate cancer is metastatic hormone resistant prostate cancer,castration naïve prostate cancer, or castration resistant prostatecancer. In some embodiments, the prostate cancer is metastatic hormoneresistant prostate cancer. In some embodiments, the prostate cancer iscarcinoma of the prostate.

In some embodiments, the cancer is ovarian cancer. In some embodiments,the cancer is carcinoma of the ovary.

In some embodiments, the cancer is AIDS-related Kaposi sarcoma.

In some embodiments, the cancer is pancreatic cancer. In someembodiments, the pancreatic cancer is adenocarcinoma of the pancreas.

In some embodiments, the cancer is bladder cancer, breast cancer,cervical cancer, esophageal cancer, gastric cancer, epithelial ovariancancer, fallopian tube cancer, primary peritoneal cancer, head and neckcancer, squamous cell carcinoma of the head and neck (SCCHN), non-smallcell lung cancer (NSCLC), castration naïve prostate cancer, castrationresistant prostate cancer, metastatic hormone resistant prostate cancer(mHRPC), small cell lung cancer, soft tissue sarcoma, or uterine cancer.

In some embodiments, the cancer is breast cancer, non-small cell lungcancer, prostate cancer (including metastatic hormone resistant prostatecancer, castration naïve prostate cancer, or castration resistantprostate cancer), squamous cell carcinoma of the head and neck, orgastric cancer.

In some embodiments, the cancer is bladder cancer, cervical cancer,ovarian cancer, epithelial ovarian cancer, fallopian tube cancer,peritoneal cancer, esophageal cancer, soft tissue sarcoma,leiomyosarcoma, uterine cancer, pancreatic cancer, or endometrialcancer.

In some embodiments, the cancer is an advanced malignancy. In someembodiments, the cancer is a primary or secondary cancer.

In some embodiments, the methods of the disclosure include a method fortreating metastatic breast cancer in a subject in need thereof, whereinthe plasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the methods of the present disclosure include amethod for treating metastatic breast cancer in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC(0→∞), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 1 to 24hours, about 1 to 20 hours, about 1-16 hours, about 2-12 hours, or about3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating non-small cell lung cancer in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC(0→∞), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating non-small cell lung cancer in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating prostate cancer (e.g., metastatic hormone resistantprostate cancer, castration naïve prostate cancer, or castrationresistant prostate cancer) in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the methods of the present disclosure include amethod for treating prostate cancer (e.g., metastatic hormone resistantprostate cancer, castration naïve prostate cancer, or castrationresistant prostate cancer) in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating adenocarcinoma of the pancreas in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating adenocarcinoma of the pancreas in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating carcinoma of the ovary in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating carcinoma of the ovary in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 1 to 24hours, about 1 to 20 hours, about 1-16 hours, about 2-12 hours, or about3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating carcinoma of the breast in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating carcinoma of the breast in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating AIDS-related Kaposi's Sarcoma in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the methods of the present disclosure include amethod for treating AIDS-related Kaposi's Sarcoma in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating metastatic breast cancer in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating metastatic breast cancer in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating non-small cell lung cancer in a subjectin need thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating non-small cell lung cancer in a subjectin need thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating adenocarcinoma of the pancreas in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating adenocarcinoma of the pancreas in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating carcinoma of the ovary in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC(0→∞), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating carcinoma of the ovary in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating carcinoma of the breast in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC(0→∞), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating carcinoma of the breast in a subject inneed thereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC(0→∞), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 1 to 24hours, about 1 to 20 hours, about 1-16 hours, about 2-12 hours, or about3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating AIDS-related Kaposi's Sarcoma in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in treating AIDS-related Kaposi's Sarcoma in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC_((0→∞)), is equal to orgreater than the plasma exposure, as measured by AUC_((0→∞)), ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 1 to 24 hours, about 1 to 20 hours, about 1-16hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingmetastatic breast cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingmetastatic breast cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80mg/m², or about 75 mg/m² over a period of about 1 to 24 hours, about 1to 20 hours, about 1-16 hours, about 2-12 hours, or about 3-8 hours onceevery three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingnon-small cell lung cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingnon-small cell lung cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingadenocarcinoma of the pancreas in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingadenocarcinoma of the pancreas in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingcarcinoma of the ovary in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingcarcinoma of the ovary in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80mg/m², or about 75 mg/m² over a period of about 1 to 24 hours, about 1to 20 hours, about 1-16 hours, about 2-12 hours, or about 3-8 hours onceevery three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingcarcinoma of the breast in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingcarcinoma of the breast in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0-w),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingAIDS-related Kaposi's Sarcoma in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hoursonce every three weeks.

In some embodiments, the present disclosure pertains to use of CompoundA in the manufacture of a medicament for use with docetaxel for treatingAIDS-related Kaposi's Sarcoma in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80mg/m², or about 75 mg/m² over a period of about 1 to 24 hours, about 1to 20 hours, about 1-16 hours, about 2-12 hours, or about 3-8 hours onceevery three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of metastatic breast cancer in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of metastatic breast cancer in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of non-small cell lung cancer in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of non-small cell lung cancer in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of adenocarcinoma of the pancreas ina subject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of adenocarcinoma of the pancreas ina subject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of g carcinoma of the ovary in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of carcinoma of the ovary in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of carcinoma of the breast in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC_((0→∞)), is equal to orgreater than the plasma exposure, as measured by AUC_((0→∞)), ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²(e.g., 75 mg/m²) over a period of about 1 to 24 hours once every threeweeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of carcinoma of the breast in asubject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of AIDS-related Kaposi's Sarcoma ina subject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC(0→∞), is equal to or greaterthan the plasma exposure, as measured by AUC(0→∞), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse with docetaxel in the treatment of AIDS-related Kaposi's Sarcoma ina subject in need thereof, wherein the plasma exposure of the orallyadministered docetaxel, as measured by AUC_((0→∞)), is equal to orgreater than the plasma exposure, as measured by AUC_((0→∞)), ofintravenously administered docetaxel (e.g., Taxotere® or docetaxelformulated with polysorbate 80) at an amount of about 60-100 mg/m²,about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75 mg/m²over a period of about 1 to 24 hours, about 1 to 20 hours, about 1-16hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofmetastatic breast cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofmetastatic breast cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofnon-small cell lung cancer in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains Compound A for usein a combination therapy with docetaxel in the treatment of non-smallcell lung cancer in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC_((0→∞)), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofadenocarcinoma of the pancreas in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofadenocarcinoma of the pancreas in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment of gcarcinoma of the ovary in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofcarcinoma of the ovary in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofcarcinoma of the breast in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(o 0.4,is equal to or greater than the plasma exposure, as measured byAUC_((0→∞)), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofcarcinoma of the breast in a subject in need thereof, wherein the plasmaexposure of the orally administered docetaxel, as measured by AUC(0→∞),is equal to or greater than the plasma exposure, as measured byAUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80 mg/m², or about 75mg/m² over a period of about 1 to 24 hours, about 1 to 20 hours, about1-16 hours, about 2-12 hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofAIDS-related Kaposi's Sarcoma in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC(0→∞), is equal to or greater than the plasma exposure, as measuredby AUC(0→∞), of intravenously administered docetaxel (e.g., Taxotere® ordocetaxel formulated with polysorbate 80) at an amount of about 60-100mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hours once everythree weeks.

In some embodiments, the present disclosure pertains to Compound A foruse in a combination therapy with docetaxel in the treatment ofAIDS-related Kaposi's Sarcoma in a subject in need thereof, wherein theplasma exposure of the orally administered docetaxel, as measured byAUC_((0→∞)), is equal to or greater than the plasma exposure, asmeasured by AUC_((0→∞)), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80mg/m², or about 75 mg/m² over a period of about 1 to 24 hours, about 1to 20 hours, about 1-16 hours, about 2-12 hours, or about 3-8 hours onceevery three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of metastatic breast cancer in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC(0→∞), is equal to or greater than the plasma exposure,as measured by AUC(0→∞), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m² (e.g., 75 mg/m²) over a period of about 1 to 24 hoursonce every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of metastatic breast cancer in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC(0→∞), is equal to or greater than the plasma exposure,as measured by AUC(0→∞), of intravenously administered docetaxel (e.g.,Taxotere® or docetaxel formulated with polysorbate 80) at an amount ofabout 60-100 mg/m², about 70-90 mg/m², about 75-85 mg/m², about 80mg/m², or about 75 mg/m² over a period of about 1 to 24 hours, about 1to 20 hours, about 1-16 hours, about 2-12 hours, or about 3-8 hours onceevery three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of non-small cell lung cancer in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC(0→∞), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of non-small cell lung cancer in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of adenocarcinoma of the pancreas in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of adenocarcinoma of the pancreas in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)) is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of carcinoma of the ovary in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of carcinoma of the ovary in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 1 to 24hours, about 1 to 20 hours, about 1-16 hours, about 2-12 hours, or about3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of carcinoma of the breast in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) over a period ofabout 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of carcinoma of the breast in a subject in need thereof,wherein the plasma exposure of the orally administered docetaxel, asmeasured by AUC_((0→∞)), is equal to or greater than the plasmaexposure, as measured by AUC_((0→∞)), of intravenously administereddocetaxel (e.g., Taxotere® or docetaxel formulated with polysorbate 80)at an amount of about 60-100 mg/m², about 70-90 mg/m², about 75-85mg/m², about 80 mg/m², or about 75 mg/m² over a period of about 1 to 24hours, about 1 to 20 hours, about 1-16 hours, about 2-12 hours, or about3-8 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of AIDS-related Kaposi's Sarcoma in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m² (e.g., 75 mg/m²) overa period of about 1 to 24 hours once every three weeks.

In some embodiments, the present disclosure pertains to a medicamentcomprising Compound A for use in a combination therapy with docetaxel inthe treatment of AIDS-related Kaposi's Sarcoma in a subject in needthereof, wherein the plasma exposure of the orally administereddocetaxel, as measured by AUC_((0→∞)), is equal to or greater than theplasma exposure, as measured by AUC_((0→∞)), of intravenouslyadministered docetaxel (e.g., Taxotere® or docetaxel formulated withpolysorbate 80) at an amount of about 60-100 mg/m², about 70-90 mg/m²,about 75-85 mg/m², about 80 mg/m², or about 75 mg/m² over a period ofabout 1 to 24 hours, about 1 to 20 hours, about 1-16 hours, about 2-12hours, or about 3-8 hours once every three weeks.

In some embodiments, the subject is fasted before docetaxel and/orCompound A is orally administered. In some embodiments, the subject isfasted for at least 3 hours, at least 4 hours, at least 6 hours, atleast 8 hours, at least 12 hours, at least 18 hours, or at least 24hours. In some embodiments, the subject is fasted for at least 12 hours,at least 18 hours, or at least 24 hours before docetaxel and/or CompoundA is orally administered.

Unless explicitly indicated otherwise, the terms “approximately” and“about” are synonymous. In some embodiments, “approximately” and “about”refer to the recited amount, dose, value (for example, AUC_((0→∞))), orduration ±20%, ±15%, ±10%, ±8%, ±6%, ±5%, ±4%, ±2%, ±1%, or ±0.5%. Inanother embodiment, “approximately” and “about” refer to the listedamount, value, or duration ±10%, ±8%, ±6%, ±5%, ±4%, or ±2%. In yetanother embodiment, “approximately” and “about” refer to the listedamount, value, or duration ±5%. In yet another embodiment,“approximately” and “about” refer to the listed amount, value, orduration ±2%. In yet another embodiment, “approximately” and “about”refer to the listed amount, value, or duration ±1%. When the terms“approximately” and “about” are used when reciting temperature ortemperature range, these terms refer to the recited temperature ortemperature range ±5° C., ±2° C., or ±1° C. In another embodiment, theterms “approximately” and “about” refer to the recited temperature ortemperature range ±2° C.

The term “docetaxel” refers to(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-ylbenzoate or N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol, CASNumber 114977-28-5, C₄₃H₅₃NO₁₄, i.e., the compound with the followingstructure:

Unless otherwise indicated, the term “docetaxel” includespharmaceutically acceptable salts and/or solvates thereof.

Docetaxel is of the chemotherapy drug class, taxane, and is asemi-synthetic analogue of paclitaxel (Taxol®), an extract from the barkof the rare Pacific yew tree, Taxus brevifolia. Docetaxel differs frompaclitaxel at two positions in its chemical structure. It has a hydroxylfunctional group on carbon 10, whereas paclitaxel has an acetate ester,and a tert-butyl carbamate ester exists on the phenylpropionate sidechain instead of the benzamide in paclitaxel.

Docetaxel suitable for intravenous administration or intravenouslyadministered docetaxel includes compositions that comprise docetaxel anda pharmaceutical excipient or carrier that facilitates the intravenousadministration of docetaxel. Such pharmaceutical excipient or carrierincludes polysorbate 80, e.g., Tween 80®. In some embodiments, thedocetaxel suitable for intravenous administration or intravenouslyadministered docetaxel includes the brand name product, TAXOTERE®, andgeneric versions thereof. In some embodiments, the docetaxel suitablefor intravenous administration or intravenously administered docetaxelincludes the brand name products, DOCEFREZ® or ZYTAX®, and genericversions thereof. In some embodiments, the docetaxel suitable forintravenous administration or intravenously administered docetaxelincludes a composition comprising protein-bound docetaxel (i.e.,nab-docetaxel or ABI-008).

Docetaxel suitable for oral administration or orally administereddocetaxel refers to a formulation of docetaxel that is administeredorally.

Liquid dosage forms for oral administration include pharmaceuticallyacceptable emulsions, microemulsions, solutions, suspensions, syrups andelixirs. In addition to the active compounds, the liquid dosage formsmay contain inert diluents commonly used in the art such as, forexample, water or other solvents, solubilizing agents and emulsifierssuch as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethylacetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyleneglycol, dimethylformamide, oils (in particular, cottonseed, groundnut,corn, germ, olive, castor, and sesame oils), glycerol,tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid estersof sorbitan, and mixtures thereof. Besides inert diluents, the oralcompositions can also include adjuvants such as wetting agents,emulsifying and suspending agents, sweetening, flavoring, and perfumingagents.

Solid dosage forms for oral administration include micro-encapsulatedactive compound forms, optionally with one or more excipients as notedabove. The solid dosage forms of tablets, dragees, capsules, pills, andgranules can be prepared with coatings and shells such as entericcoatings, release controlling coatings and other coatings well known inthe pharmaceutical formulating art. In such solid dosage forms theactive compound may be admixed with at least one inert diluent such assucrose, lactose or starch. Such dosage forms may also comprise, as isnormal practice, additional substances other than inert diluents, e.g.,tableting lubricants and other tableting aids such a magnesium stearateand microcrystalline cellulose. In the case of capsules, tablets andpills, the dosage forms may also comprise buffering agents.

In some embodiments, the orally administered docetaxel is in capsuleform. In some embodiments, each capsule contains docetaxel and asurfactant, e.g., polysorbate 80. In some embodiments, each capsulecontains 30 mg-200 mg of docetaxel. In some embodiments, each capsulecontains 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175mg, or 200 mg of docetaxel. In some embodiments, each capsule contains30 mg of docetaxel. In some embodiments, each capsule contains 500 mg ofpolysorbate 80. In some embodiments each capsule contains 30 mg ofdocetaxel and 500 mg of polysorbate 80. In some embodiments, the orallyadministered docetaxel is in tablet form. In some embodiments, eachtablet contains 30 mg-200 mg of docetaxel. In some embodiments, eachtablet contains 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, 100 mg, 125 mg, 150mg, 175 mg, or 200 mg of docetaxel. In some embodiments, each tabletcontains 30 mg of docetaxel. In some embodiments, the orallyadministered docetaxel is in solution form. In some embodiments, eachsolution contains 30 mg-200 mg of docetaxel. In some embodiments, eachsolution contains 30 mg, 45 mg, 60 mg, 75 mg, 90 mg, 100 mg, 125 mg, 150mg, 175 mg, or 200 mg of docetaxel. In some embodiments, each solutioncontains 30 mg of docetaxel.

Oral formulation of docetaxel (e.g., capsule, tablet, or solution) maybe formulated by any suitable methods known in the art.

The term “Compound A” refers to a compound, or a pharmaceuticallyacceptable salt and/or solvate thereof, which is a P-gp pump inhibitorand has the following structure:

Unless indicated otherwise, the terms “Compound A,” “HM30181methanesulfonate monohydrate,” “HM30181A,” “HM30181 AK,” and“HM30181AK-US” are all equivalent and are used interchangeably. In someembodiments, Compound A refers to a methanesulfonate salt monohydrate ofCompound A.

In some embodiments, Compound A refers to a methanesulfonate saltmonohydrate of Compound A. Compound A is commercially available, e.g.,in tablet form suitable for oral administration. In some embodiments,Compound A is administered in 15 mg tablets suitable for oraladministration.

Compound A may be formulated by any suitable methods known in the art.

The term “subject” includes any living organism that has cancer or is ata risk of developing cancer. In some embodiments, the term “subject”refers to a mammal that has cancer or is at a risk of developing cancer.In some embodiments, the term subject refers to a human being that hascancer or is at a risk of developing cancer. In some embodiments, theterm subject refers to a cancer patient, i.e., a patient.

The term “AUC_((0→∞))” refers to the total exposure to a drug and isexpressed in unit of concentration time. In some embodiments, it is theconcentration of a drug over a time interval circulating in the body,e.g., in the plasma, blood, or serum. In some embodiments,AUC_((0→∞))=AUC_((0→Tlast))+(C_(Tlast)/K_(elim)), where C_(Tlast) is thelast measureable measurable drug concentration and K_(elim) is theterminal elimination rate constant, expressed in time⁻¹ units.

In some embodiments, C_(Tlast) may be determined from about 1 day toabout 21 days after oral administration of docetaxel.

In some embodiments, C_(Tlast) may be determined from about 2 days toabout 14 days after oral administration of docetaxel.

In some embodiments, C_(Tlast) may be determined from about 3 days toabout 7 days after oral administration of docetaxel.

In some embodiments, C_(Tlast) may be determined at about 2 days afteroral administration of docetaxel. In some embodiments, C_(Tlast) may bedetermined at about 3 days after oral administration of docetaxel. Insome embodiments, C_(Tlast) may be determined at about 4 days after oraladministration of docetaxel. In some embodiments, C_(Tlast) may bedetermined at about 5 days after oral administration of docetaxel. Insome embodiments, C_(Tlast) may be determined at about 6 days after oraladministration of docetaxel. In some embodiments, C_(Tlast) may bedetermined at about 7 days after oral administration of docetaxel.

Hematologic toxicity associated with the intravenous administration ofdocetaxel in a subject suffering from cancer can be assessed by amedical professional or health care worker by analyzing blood samples ina subject, i.e., determining cell counts, including white blood cells,absolute neutrophils, platelets, and hemoglobin.

Hypersensitivity-type infusion reactions, and symptoms associated withhematologic toxicity and/or neurotoxicity associated with theintravenous administration of docetaxel in a subject suffering fromcancer can be assessed by a medical professional or health care worker.

As used herein, the phrase “pharmaceutically acceptable” refers to thosecompounds, materials, compositions, carriers, and/or dosage forms whichare, within the scope of sound medical judgment, suitable for use incontact with the tissues of human beings and animals without excessivetoxicity, irritation, allergic response, or other problem orcomplication, commensurate with a reasonable benefit/risk ratio.

The term “QD” refers to every day, the term “Q1W” refers to every oneweek, the term “Q2W” refers to every two weeks, and the term “Q3W”refers to every three weeks.

The term “QDx2” refers to on day 1 and day 2 weekly, the term “QDx3”refers to on day 1-day 3 weekly, the term “QDx4” refers to on day 1-day4 weekly, the term “QDx5” refers to on day 1-day 5 weekly, and the term“QDx6” refers to on day 1-day 6 weekly.

The term “oral docetaxel”, as used herein, refers to docetaxeladministered as oral formulations, as described herein, in combinationwith Compound A, as described herein.

“Pharmaceutically acceptable excipient” means an excipient that isuseful in preparing a pharmaceutical composition that is generally safe,non-toxic and neither biologically nor otherwise undesirable, andincludes excipient that is acceptable for veterinary use as well ashuman pharmaceutical use. A “pharmaceutically acceptable excipient” asused in the specification and claims includes both one and more than onesuch excipient.

The term “therapeutically effective amount”, as used herein, refers toan amount of a pharmaceutical agent to treat, ameliorate, or prevent anidentified disease or condition, or to exhibit a detectable therapeuticor inhibitory effect. The effect can be detected by any assay methodknown in the art. The precise effective amount for a subject will dependupon the subject's body weight, size, and health; the nature and extentof the condition; and the therapeutic or combination of therapeuticsselected for administration. Therapeutically effective amounts for agiven situation can be determined by routine experimentation that iswithin the skill and judgment of the clinician.

For any compound, the therapeutically effective amount can be estimatedinitially either in cell culture assays or in animal models, usuallyrats, mice, rabbits, dogs, or pigs. The animal model may also be used todetermine the appropriate concentration range and route ofadministration. Such information can then be used to determine usefuldoses and routes for administration in humans. Therapeutic/prophylacticefficacy and toxicity may be determined by standard pharmaceuticalprocedures in cell cultures or experimental animals, e.g., ED₅₀ (thedose therapeutically effective in 50% of the population) and LD₅₀ (thedose lethal to 50% of the population). The dose ratio between toxic andtherapeutic effects is the therapeutic index, and it can be expressed asthe ratio, LD₅₀/ED₅₀. Pharmaceutical compositions that exhibit largetherapeutic indices are preferred. The dosage may vary within this rangedepending upon the dosage form employed, sensitivity of the patient, andthe route of administration.

Dosage and administration are adjusted to provide sufficient levels ofthe active ingredient or to maintain the desired effect. Factors whichmay be taken into account include the severity of the disease state,general health of the subject, age, weight, and gender of the subject,diet, time and frequency of administration, drug combination(s),reaction sensitivities, and tolerance/response to therapy. Long-actingpharmaceutical compositions may be administered every 3 to 4 days, everyweek, or once every two weeks depending on half-life and clearance rateof the particular formulation.

The pharmaceutical compositions containing docetaxel may be manufacturedin a manner that is generally known, e.g., by means of conventionalmixing, dissolving, granulating, dragee-making, levigating, emulsifying,encapsulating, entrapping, or lyophilizing processes. Pharmaceuticalcompositions may be formulated in a conventional manner using one ormore pharmaceutically acceptable carriers comprising excipients and/orauxiliaries that facilitate processing of the active ingredient intopreparations that can be used pharmaceutically. Of course, theappropriate formulation is dependent upon the route of administrationchosen.

Pharmaceutical compositions suitable for injectable use include sterileaqueous solutions (where water soluble) or dispersions and sterilepowders for the extemporaneous preparation of sterile injectablesolutions or dispersions. For intravenous administration, suitablecarriers include physiological saline, bacteriostatic water, CremophorEL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In allcases, the composition must be sterile and should be fluid to the extentthat easy syringeability exists. It must be stable under the conditionsof manufacture and storage and must be preserved against thecontaminating action of microorganisms such as bacteria and fungi. Thecarrier can be a solvent or dispersion medium containing, for example,water, ethanol, polyol (for example, glycerol, propylene glycol, andliquid polyethylene glycol, and the like), and suitable mixturesthereof. The proper fluidity can be maintained, for example, by the useof a coating such as lecithin, by the maintenance of the requiredparticle size in the case of dispersion and by the use of surfactants.Prevention of the action of microorganisms can be achieved by variousantibacterial and antifungal agents, for example, parabens,chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In manycases, it will be preferable to include isotonic agents, for example,sugars, polyalcohols such as manitol, sorbitol, sodium chloride in thecomposition. Prolonged absorption of the injectable compositions can bebrought about by including in the composition an agent which delaysabsorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by incorporating docetaxelin the required amount in an appropriate solvent with one or acombination of ingredients enumerated above, as required, followed byfiltered sterilization. Generally, dispersions are prepared byincorporating form docetaxel into a sterile vehicle that contains abasic dispersion medium and the required other ingredients from thoseenumerated above. In the case of sterile powders for the preparation ofsterile injectable solutions, methods of preparation are vacuum dryingand freeze-drying that yields a powder of docetaxel plus any additionaldesired ingredient from a previously sterile-filtered solution thereof.

Oral compositions generally include an inert diluent or an ediblepharmaceutically acceptable carrier. They can be enclosed in gelatincapsules or compressed into tablets. For the purpose of oral therapeuticadministration, form can be incorporated with excipients and used in theform of tablets, troches, or capsules. Oral compositions can also beprepared using a fluid carrier for use as a mouthwash, wherein in thefluid carrier is applied orally and swished and expectorated orswallowed. Pharmaceutically compatible binding agents, and/or adjuvantmaterials can be included as part of the composition. The tablets,pills, capsules, troches and the like can contain any of the followingingredients, or compounds of a similar nature: a binder such asmicrocrystalline cellulose, gum tragacanth or gelatin; an excipient suchas starch or lactose, a disintegrating agent such as alginic acid,Primogel, or corn starch; a lubricant such as magnesium stearate orSterotes; a glidant such as colloidal silicon dioxide; a sweeteningagent such as sucrose or saccharin; or a flavoring agent such aspeppermint, methyl salicylate, or orange flavoring.

The pharmaceutical compositions described herein can be included in acontainer, pack, or dispenser together with instructions foradministration.

All percentages and ratios used herein, unless otherwise indicated, areby weight.

Other features and advantages of the present disclosure are apparentfrom the different examples. The provided examples illustrate differentcomponents and methodology useful in practicing the present disclosure.

The examples do not limit the claimed disclosure. Based on the presentdisclosure the skilled artisan can identify and employ other componentsand methodology useful for practicing the present disclosure.

EXAMPLES Example 1—Clinical Study of Orally Administered Docetaxel inCombination with Compound A in Comparison to IV Docetaxel

A 2-part study was conducted in subjects with metastatic prostate cancer(“Study 1”). The initial stage included a 21-day cycle of IVadministered docetaxel (at the dose prescribed for each participant astheir prior final treatment with IV docetaxel). In the second part ofthis study, oral docetaxel, starting at 75 mg/m², 150 mg/m², or 225mg/m² was administered as a single dose. A total of 5 (n=18) subjectsenrolled in this study.

The area under the curve from 0 to 24 hours (AUC₀₋₂₄) was higher for IVadministration in comparison to oral dosage. Docetaxel plasmaconcentrations showed an increase with IV dose (35, 75 mg/in²). The dosenormalized AUC for IV and oral dosage was 27.17 (ng*hr/mL) and 23.33(ng*hr/mL), respectively. The half-life (tin) for oral docetaxel was21.3 h, comparable to that of IV docetaxel at 21.9 h. The results areshown in Table 1 and in FIGS. 1 and 2 . Additional pharmacokinetic IVversus oral dosage comparison is shown in Tables 2 and 3 and FIGS. 4 and5 .

TABLE 1 Oral and IV docetaxel pharmacokinetics Length of Dose Dose No.of infusion C_(max) AUC₀₋₂₄ Normalized t_(1/2) (mg/m²) patients (h)(ng/mL) (ng*hr/mL) AUC (h) 60 3 1 1310 1630 (19.2%) 27.17 21.9 mg/m²(21.1%) (313) IV (276) 75 3 NA  103  329 (4.0%) 23.33 21.3 mg/m² (18.7%)(13.1) Oral (19.3)

TABLE 2 Pharmacokinetics summary of oral docetaxel (C_(max), T_(max),t_(1/2)) C_(max) (ng/mL) T_(max) t_(1/2)( hr⁻¹) IV IV IV Subject Oraldocetaxel docetaxel Oral docetaxel docetaxel Oral docetaxel docetaxel 185.60 1573.42 2.00 1.00 16.51 16.82 3 99.49 1324.69 2.50 0.98 20.9921.65 4 123.64 1022.69 1.00 0.67 25.80 22.03 Mean 102.91 1306.93 1.830.88 21.10 20.17 SD 19.25 275.79 0.76 0.19 4.65 2.91 CV % 18.71 21.1041.66 21.26 22.02 14.41 Mean % 7.87 207.55 104.60 Max 123.64 1573.422.50 1.00 25.08 22.03 Min 85.60 1022.69 1.00 0.67 16.51 16.82

The mean C_(max) for oral and IV docetaxel showed 102.91 and 1306.93ng/mL, respectively. Oral docetaxel showed a maximum C_(max) of 123.64and a minimum of 85.60 ng/mL IV docetaxel showed a maximum C_(max) of1573.42 and a minimum of 1022.69 ng/mL. The mean T_(max) for oral and IVdocetaxel showed 1.83 and 0.88 hr respectively. Oral docetaxel showed amaximum T_(max) of 2.50 and a minimum of 1.00 hr. IV docetaxel showed amaximum T_(max) of 1.00 and a minimum of 0.67 hr. The mean t_(1/2) fororal and IV docetaxel showed 21.10 and 20.17 hr⁻¹, respectively. Oraldocetaxel showed a maximum t_(1/2) of 25.08 and a minimum of 16.51 hr⁻¹.IV docetaxel showed a maximum t_(1/2) of 22.03 and a minimum of 16.82hr⁻¹. The results are shown in Table 2.

TABLE 3 PK summary of oral docetaxel (AUC_(0-t), AUC_(0-inf), AbsoluteBioavailability) AUC_(0-t) (ng*hr/mL) AUC_(0-inf) (ng*hr/mL) AbsoluteOral IV Oral IV Bioavailability Subject docetaxel docetaxel docetaxeldocetaxel (%) 1 339.37 2226.82 402.64 2291.49 12.30 3 361.10 1741.59442.31 1822.04 17.80 4 484.69 1714.69 589.65 1801.79 25.09 Mean 395.051894.37 478.20 1971 77 18.40 SD 78.38 288.23 98.54 277.06 6.42 CV %19.84 15.21 20.61 14.05 34.87 Mean % 20.85 24.25 Max 484.69 2226 82589.65 2291.49 25.09 Min 339.37 1714.69 402.64 1801.79 12.30

The mean AUC_(0-t) or oral and IV docetaxel showed 395.02 and 1894.37ng*mL, respectively. Oral docetaxel showed a maximum AUC_(0-t) of 484.69and a minimum of 339.37 ng*hr/mL. IV docetaxel showed a maximumAUC_(0-t) of 2226.82 and a minimum of 1714.69 ng*hr/mL. The meanAUC_(0-inf) for oral and IV docetaxel showed 478.20 and 1971.77ng*hr/mL, respectively. Oral docetaxel showed a maximum AUC_(0-inf) of589.65 and a minimum of 402.64 ng*hr/mL. IV docetaxel showed a maximumAUC_(0-inf) of 2291.49 and a minimum of 1801.79 ng*hr/mL. The meanabsolute bioavailability showed 18.40%, with a maximum of 25.09% and aminimum of 12.30%. The results are shown in Table 3.

Example 2—Clinical Study of Orally Administered Docetaxel in Combinationwith Compound A—Dosage Investigation of Solid Tumors

A 2-part study was conducted in subjects with solid tumors (“Study 2”).The initial stage included a 21-day 3+3 dose escalation to maximumtolerated dose (MTD) of oral docetaxel, at a starting dose of 35 mg/m².The dose levels increased to 75 mg/m², 150 mg/m², 225 mg/m², 300 mg/m²,375 mg/m², and 400 mg/m². In the second part of this study, half of thegroup starting at a selected dose from stage 1, was given over twoconsecutive days every three weeks. A total of 15 (n=40) subjectsenrolled in this study.

Pharmacokinetic results from the 2 studies showed that the maximumconcentration C_(max) value for 35 mg/m², 75 mg/m², and 150 mg/m² doseswere 69.1 ng/mL, 172 ng/mL, and 124 ng/mL, respectively. The area underthe curve from 0 to 24 hours (AUC₀₋₂₄) increased with dosage increasewith 263 ng*hr/mL for 35 mg/m² oral docetaxel, 598 ng*hr/mL for 75 mg/m²oral docetaxel, and 753 ng*hr/mL for 150 mg/m² oral docetaxel. The dosenormalized AUC decreased with increase of oral dosage of oral docetaxelfrom 39.97 to 26.70 from 35 mg/m² to 150 mg/m², respectively. Thehalf-life (t_(1/2)) for oral dosed oral docetaxel increased withincreased dosage from 29.2 h to 53.1 h to 62.8 h, respectively for 35mg/m², 75 mg/m², and 150 mg/m². The differences in half-life for thesestudies can be attributed to different sampling schedules. The resultsare shown in Tables 4 and 5, as well as in FIGS. 1 and 2 .

TABLE 4 Oral docetaxel pharmacokinetics across a dosage range DoseLength of C_(max) AUC₀₋₂₄ Dose (mg/m²) No. of patients infusion (h)(ng/mL) (ng*hr/mL) Normalized AUC t_(1/2) (h)  35 mg/m² 4 NA  69.1 263(43.7%) 39.97 29.2 Oral (92.9%) (115) (64.2)  75 mg/m² 3 NA 172 598(63.9%) 38.23 53.1 Oral (54.8%) (382) (94.4) 150 mg/m² 5 NA 124 753(37.4%) 26.70 62.8 Oral (9.66%) (306) (12.0)

TABLE 5 Docetaxel pharmacokinetics summary AUC % Dose C_(max) T_(max)AUC₀₋₂₄ AUC_(last) AUC_(inf)_obs t_(1/2) Extrap_obs (mg) (ng/mL) (hr)(hr*ng/mL) (hr*ng/mL) (hr*ng/mL) (hr) (%) R_(sq)_adjusted  35 N 4 4 4 44 4 4 4 Mean 69.1 1.50 211 276 296 27.6 7.51 0.975 CV % 92.9 38.5 67.876.8 77.2 95.7 43.8 2.17  75 N 3 3 3 3 3 3 3 Mean 172 2.00 598 788 81553.1 3.89 0.993 CV % 54.8 0.00 63.9 60.4 59.1 15.6 31.8 0.303 150 N 3 33 3 3 3 3 3 Mean 124 2.67 753 931 976 62.8 4.48 0.969 CV % 9.66 43.337.2 36.4 37.3 15.0 37.8 3.01 225 N 3 3 3 3 3 3 3 3 Mean 114 1.00 7921120 1190 56.0 4.93 0.964 CV % 24.0 86.6 41.2 49.3 50.0 19.1 35.2 3.17

Docetaxel pharmacokinetics increase with dose. The area under the curveextrapolated to infinity (AUC_(inf)) shows an increase with the increaseof dose. PK data indicates that oral docetaxel exposure increases withdose and that exposure similar to that achieved with IV dosing isfeasible with 1 or 2 days of dosing every three week.

Individual and cohort pharmacokinetic data is shown in Tables 11 and 12,and FIGS. 6-12B.

Example 3—A Comparison of Pharmacokinetic Properties of OralAdministration of Docetaxel in Combination with Compound A Studies(Study 1 and Stud

IV docetaxel plasma concentrations increase with dose. Oral docetaxelhas similar PK profiles across both studies. The results are shown inTables 6 and 7.

TABLE 6 Summary of Docetaxel PK Parameters Dose C_(max) AUC_(0-inf)Study Route (mg/m²) (ng/ml) (ng*hr/mL) Study 1 IV  60  131 (21.1%) 1920(13.2%) N = 3 Oral  75  103 (18.7%)  476 (20.8%) N = 3 Study 2 Oral  3569.1 (92.9%)  308 (90.4%) N = 4 (N = 3)  75  172 (54.8%)  756 (50.9%) N= 3 150  124 (9.66%)  976 (37.3%) N = 3

TABLE 7 Study 1 and Study 2 Comparison Stratified by Cancer DiagnosisCancer C_(max) AUC₀₋₂₄ Study Dose (mg/m²) Screening # Subject #Diagnosis (ng/mL) (ng*hr/mL) Study 2  35 001-S001 001-101 Lung ND  35001-S003 001-102 Breast 73.0 227  35 001-S004 001-103 Esophagus 157 392001-S007 N/A Lung  35 002-S001 002-104 Urothelial 38.0 170 002-S002 N/AUrothelial  75 001-S006 001-201 Pancreatic 165 461 002-S003 N/A Cervix 75 002-S004 002-203 Ovarian 81.6 304  75 002-S005 003-203 Ovarian  75003-S001 003-202 IVC high grade 190 1030 leiomyosarcoma 150 001-S008001-302 Pancreas 125 1050 150 002-S007 002-303 Endometrium 136 720 150003-S002 003-301 Neck of 112 490 Pancreas Study 1  60 (IV)  1 Prostate1570 1970  60 (IV)  3 1320 1570  60 (IV)  4 1020 1350  75  1 85.6 313 75  3 99.5 336  75  4 124 336

In Study 1, all subjects had a diagnosis of prostate cancer. An oraldosage of 75 mg/m² showed a C_(max) in the range of 85.6-124 ng/mL andan AUC₀₋₂₄ of 313-336 ng*hr/mL. An IV dosage of 60 mg/m² showed a C inthe range of 1020-1570 ng/mL and an AUC₀₋₂₄ of 1350-1970 ng*hr/mL.

In Study 2, the cancers diagnoses included lung, breast, esophagus,lung, urothelial, pancreatic, cervix, ovarian, and IVC high gradeleiomyosarcoma. An oral dosage of 75 mg/n showed a C_(max) in the rangeof 81.6-190 ng/mL and an AUC₀₋₂₄ of 304-1030 ng*hr/mL, varied by cancerdiagnosis. An oral dosage of 335 mg/m² showed a C_(max) in the range of38.0-157 ng/mL and an AUC₀₋₂₄ of 170-392 ng*hr/mL, varied by cancerdiagnosis. An oral dosage of 150 mg/m² showed a C_(max) in the range of112-136 ng/mL and an AUC₀₋₂₄ of 490-1050 ng*hr/mL, varied by cancerdiagnosis. The results are shown in Table 4.

Table 8 shows the half life comparison between Study 1 oral docetaxeland IV docetaxel. Additionally, Table 8 shows the comparison of halflife for Study 2 across a range of doses. Both IV and oral docetaxel ofstudy 1 show comparable reported half-lives.

TABLE 8 Half-life comparison of Study 1 and 2 Dose Study LLOQ regimen PKSampling Reported half-life 1 NA  75 mg/m² Predose, 0.25, 0.5, 0.75, 75mg/m²: 16.4, (oral) 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 21.4, 26.0 h 4, 5, 6,8, 12, 18, 24, 32, 48, 56, 72, 96  60 mg/m² Predose, 2, 5, 8, 12, 20, 60mg/m²: 17.4, (iv) 40, 60 min during 18.4, 30.1 h infusion, 0.25, 0.5,0.75, 1, 2, 3, 4, 6, 8, 12, 18, 24, 32, 48, 56, 72 hours post infusion 20.2  35 mg/m² Predose docetaxel, 0.25, 35 mg/m²: 3.4 h, ng/mL  75 mg/m²0.5, 1, 2, 4, 6, 8, 12, 24, 19.1 h, 65.3 h 150 mg/m² 48, 72, 168(docetaxel 75 mg/m²: 51.4 h, sampling points) 62.4 h, 45.8 h 150 mg/m²:72.0 h, 53.3 h, 63.3 h

Table 9 outlines the clinical study protocols for both Study 1 and Study2.

TABLE 9 Clinical Study Protocol Study 1 Study 2 Inclusion Men only Menand Women (currently, Criteria mostly women are enrolled) CancerMetastatic Prostate Any advanced solid Diagnosis Cancer onlymalignancies Permissible Steroids are allowed Steroids are restricted toConMeds only specific cases PK Sampling Predose Docetaxel, 0.25, PredoseHM30181A, time points 0.5, 0.75, 1, 1.25, 1.5, 2, Predose Docetaxel,0.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 18,24, 32, 48, 56, 72, 96 72, 168, 336 (HM only), 504 (HM only)Pre-medication Per PI discretion Restricted to specific cases Inclusion≥90 g/L(9 g/dL) ≥10 g/dL criteria for HGB Fasting 8 hours before and 6hours before and 2 hours requirements 4 hours after dosing after dosingCaffeine/ Restricted for 3 days and Not restricted Alcohol 12 hours,respectively Water intake Not restricted Restricted to less than withdosing 240 mL

Example 4—Target Concentration of Orally Administered Docetaxel

A target concentration was determined based upon GI₅₀ from screeningNCI-60 cell lines with docetaxel (NCI-60 cell line screen of Docetaxel;Braakhuis et al. Anticancer Research (1994) 14: 205-208.; Engblom et al.Anticancer Research (1997) 17: 2475-2480.; Kelland et al. CancerChemother Pharmacol (1992) 30: 444-450.; Riccardi et al. Eur J of Cancer(1995) 31A: 494-499.). The IC₅₀ range from 0.5 to 5 nM was targeted withcorresponding docetaxel plasma concentrations from 0.4 to 4 ng/mL.Individuals administered 35 or 75 mg/in² oral docetaxel surpassed the invitro target IC₅₀ of 5 nM (4 ng/mL), Table 10 shows the standard timeabove the targeted IC₅₀ for each study and dose regimen.

TABLE 10 Time above target IC₅₀: comparisons of Study 1 and Study 2Average Time above Target (h) (0 to last time point measured above Dose(mg/m²) Regimen 4 ng/ml) Study 60 1 h IV infusion Q3W 40.9 1 35 SD 75 275 SD 20.5 1 75 SD 21.5 2 150 SD 15.5 2

The known efficacious monotherapy schedule for mHRPC, was utilized todetermine the target AUC for 75 mg/m² over 28 days as 3410+/−980 h*ng/mL(Baker et al 2004, mixed solid tumours). The provided PK data isequivalent in mHRPC. Dosages were extrapolated from Baker et al throughtargeting desired concentrations from various IV docetaxel regimens,seen in FIG. 3 .

Utilizing predicted mean AUC pre cycle from Study 2 to replicate thetarget AUC over three weeks the oral docetaxel dosage would accordinglybe 150 mg/m² dosed for 4 days of a three week schedule or 75 mg/m² dosedfor 5 days of a three week schedule. Additionally, the desired AUC maybe matched by 225 mg/m² dosed for 2 to 3 days of a three week schedule,or 1 day every three weeks.

Example 5—Oral Docetaxel Exposure

Oral docetaxel was administered twice per week, on consecutive days overa 21 day period. Compound A was administered once before oraladministration of docetaxel. Two models of data were presented topredict oral docetaxel AUC versus dose.

NCA Procedure

All subject PK data within the dataset were analyzed using Phoenix 8.0.NCA Model “Plasma (200-202)” with extravascular dose input selectedwithin the software. Individual time points for the terminal slope wereautomatically selected by the software, and linear up-log downinterpolation calculation method was used for the analysis. IndividualBLQ samples were set to 0.00 ng/ml for noncompartmental analysis unlessthe PK sample occurred between two PK samples above the limit ofquantification, in which case the PK sample was set to missing. For thecalculation of summary statistics and mean concentration figures, allBLQ samples were set to 0.00 ng/ml. If the extrapolated portion ofAUC_(0-∞) from time of last measurable plasma concentration to infinity(AUC % extrap) for a subject was greater than 20.0% or the adjusted R²was less than 0.85, the AUC_(0-∞) dependent parameters were notreported. If R² was less than 0.85, the t_(1/2) was not reported.

TABLE IL Study 2 docetaxel individual subject and summary PK parameterdata AUC₀₋₁₂ AUC₀₋₂₄ AUC₀₋₄₈ AUC_(last) CL/F AUC Dose Cmax Tmax (hr*ng/(hr*ng/ (hr*ng/ (hr*ng/ T_(1/2) AUC_(INF)_obs (L/hr/ Vd/F Extrap_(obs)Rsq_ Analyte (mg/m²) ID (ng/mL) (hr) mL) mL) mL) mL) (hr) (hr*ng/mL) m²)(L/m²) (%) adjusted Docetaxel  35 1 8.59 1.00 39.8 46.1 46.1 39.8 3.4044.9 779 3820 11.4 0.992 2 73.0 1.00 198 227 257 270 19.1 279 125 34503.39 0.995 3 157 2.00 353 392 440 554 65.3 599 58.4 5500 7.45 0.954 438.0 2.00 145 178 218 239 22.8 259 135 4440 7.76 0.961 N 4 4 4 4 4 4 4 44 4 4 4 Mean 69.1 1.50 184 211 240 276 27.6 296 274 4300 7.51 0.975 CV %92.9 38.5 70.8 67.8 67.2 76.8 95.7 77.2 123 20.9 43.8 2.17 Docetaxel  755 165 2.00 390 461 543 660 51.4 690 109 8060 4.31 0.996 6 81.6 2.00 270304 334 389 62.1 409 183 16400 4.87 0.992 7 270 2.00 875 1030 1150 131045.8 1350 55.7 3680 2.50 0.990 N 3 3 3 3 3 3 3 3 3 3 3 3 Mean 172 2.00512 598 675 788 53.1 815 116 9390 3.89 0.993 CV % 54.8 0.00 62.6 63.962.6 60.4 15.6 59.1 55.4 69.0 31.8 0.303 Docetaxel 150 8 125 2.00 8981050 1150 1300 72.0 1380 109 11300 5.59 0.938 9 136 4.00 650 720 775 85453.2 876 171 13100 2.53 0.973 10 112 2.00 446 490 538 637 63.3 673 22320300 5.32 0.996 N 3 3 3 3 3 3 3 3 3 3 3 3 Mean 124 2.67 665 753 819 93162.8 976 168 14900 4.48 0.969 CV % 9.66 43.3 34.1 37.2 37.4 36.4 15.037.3 34.1 32.0 37.8 3.01 Docetaxel 225 11 118 2.00 835 986 1100 130067.3 1390 161 15700 6.48 0.950 12 139 0.500 380 416 443 501 54.4 517 43634200 3.06 0.999 13 84.7 0.500 637 974 1200 1560 46.1 1650 137 9100 5.260.944 N 3 3 3 3 3 3 3 3 3 3 3 3 Mean 114 1.00 618 792 914 1120 56.0 1190245 19700 4.93 0.964 CV % 24.0 86.6 36.9 41.2 45.0 49.3 19.1 50.0 67.866.2 35.2 3.17

TABLE 12 Study 2 docetaxel individual concentration vs time table Time(hr) 0.00 0.250 0.500 1.00 2.00 4.00 6.00 8.00 12.0 24.0 48.0 72.0 168An- Dose Co- Analyte Concentration alyte (mg/m²) hort SUBJID (ng/ml)Doc-  35 1  1 BLQ BLQ  1.80  8.59  5.05  4.55  3.52  2.52  1.05 BLQ BLQBLQ BLQ etaxel  2 BLQ  73.0  50.4  10.7  8.60  5.23  3.17  1.82 0.344BLQ  3 BLQ BLQ  2.94  82.8 157  20.8  12.1  7.66  4.92  2.00 2.02 1.230.474  4 BLQ BLQ  0.383  7.14  38.0  25.3  7.87  4.92  3.20  1.25 0.6750.612 BLQ Doc-  75 2  5 BLQ BLQ  25.3  61.2 165  24.4  15.2 12.9  6.67 5.22 2.08 1.39 0.401 etaxel  6 BLQ BLQ  13.7  52.8  81.6  35.3  9.07 5.99  4.32  1.75 0.872 0.612 0.222  7 BLQ 28.0 190 164 270  79.5  35.714.0 21.7  6.94 3.28 1.99 0.510 Doc- 150 3  8 BLQ  0.319  21.3  20.6 125ALQ 104 76.6 22.3  6.09 2.53 1.62 0.742 etaxel  9 BLQ BLQ  15.1  37.6116 136  41.3 32.8  9.07  3.38 1.47 0.890 0.289 10 BLQ  2.90  23.6 111112  57.9  18.0 13.1  5.05  2.63 1.43 1.17 0.392 Doc- 225 4 11 BLQ BLQ 2.14  55.6 118 ALQ  95.1 61.4 22.6  6.06 3.43 2.18 0.931 etaxel 12 BLQ 8.40 139 105  90.4  28.0  13.9 11.1  5.22  1.43 0.917 0.696 0.201 13BLQ  3.19  84.7  54.4 ALQ ALQ ALQ ALQ 53.2 12.4 7.17 3.90 1.30

TABLE 13 IV docetaxel pharmacokinetics Dose No. of Length of CmaxAUC₀₋₂₄ Dose Normalized t_(1/2) (mg/m²) patients infusion (h) (ng/ml)(ng*hr/mL) AUC γ (h)  20 (n = 1) 1  1  960 48  2.2  20 (n = 1) 1 24  92046  30 (n = 2) 2  1.58 (0.80)  640 (450) 1260 (340) 42  4.6 (2.8)  40 (n= 1) 1  1  420  670 16.75  3.8  40 (n = 3) 3 24 2190 (2140-2240)* 54.75 55 (n = 3) 3  1.68 (0.75)  820 (380) 1420 25.82  2  55 (n = 4) 4 242560 (1190-3280)* 46.55  70 (n = 2) 2  1.37 (0.53) 1910 (320) 2790 (850)39.86  2.5 (1.4)  70 (n = 3) 3 24 3470 (2900-4510)* 49.57  85 (n = 6) 6 1.61 (0.81) 2420 (920) 4100 (920) 48.24 13.6 (6.1)  90 (n = 5) 5 247810 (5950-9820)* 86.78 100 (n = 4) 4  2.03 (0.09) 2410 (250) 5930 (530)59.30 18.5 (10.7) 115 (n = 4) 4  1.84 (0.28) 2680 (930) 5190 (160) 45.13 9.6 (5.8)

Example 6—Oral Dosing of Docetaxel Capsules in Combination with HM30181A

Two phase 1 studies were performed to investigate the pharmacokineticsand tolerability of docetaxel capsules administered orally incombination with HM30181A. In a first study, the absolutebioavailability and AUC of oral docetaxel 75 mg/m² (n=3) administeredwith 15 mg HM30181A was determined. In a second study, thepharmacokinetics of oral docetaxel was determined at doses of 35, 75,150 and 225 mg/m² in combination with HM30181A 15 mg in groups of 3-6patients with advanced cancer.

In combination with HM30181A, the docetaxel was rapidly absorbed withmean T_(max) of 3-4 hours. The C_(max) and AUC increased with dose from35 to 225 mg/m². The AUC for IV (75 mg/m²) and oral (35, 75, 150, and225 mg/m²) were 2422, 248, 692, 888, and 1400 ng·hr/mL, respectively.Individual F % ranged between 20-31% at a dose of 75 mg/m². C_(max) wasat 9.5-13% of that observed after IV administration. The terminal phasehalf-life is approximately 56 hours. Based on non-linear regressionanalysis, oral administration at 75 mg/m² for three days or 150 mg/m²for two days is calculated to achieve similar AUC compared to IVdocetaxel (75 mg/m²). Thus, short-term oral administration of docetaxeland HM30181A can achieve a similar AUC with a lower C_(max) comparedwith IV docetaxel (75 mg/m²), showing promising activity andtolerability for this combination.

EQUIVALENTS

The details of one or more embodiments of the invention are set forth inthe accompanying description above. Although any methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present disclosure, the preferred methods andmaterials are now described. Other features, objects, and advantages ofthe present disclosure will be apparent from the description and fromthe claims. In the specification and the appended claims, the singularforms include plural referents unless the context clearly dictatesotherwise. Unless defined otherwise, all technical and scientific termsused herein have the same meaning as commonly understood by one ofordinary skill in the art to which this disclosure belongs. All patentsand publications cited in this specification are incorporated byreference.

The foregoing description has been presented only for the purposes ofillustration and is not intended to limit the invention to the preciseform disclosed, but by the claims appended hereto.

1.-127. (canceled)
 128. A method for treating cancer in a subject in need thereof, comprising: a. oral administration of docetaxel at an amount of about 15 mg/m² to about 450 mg/m² to the subject once a day and for 1-7 times a week; and b. oral administration of Compound A:

to the subject once a day and for 1-7 times a week, and wherein Compound A is administered simultaneously with or prior to the docetaxel.
 129. A method for reducing hematologic toxicity and/or neurotoxicity, and/or other toxicities or symptoms in a subject suffering from cancer and undergoing docetaxel therapy, comprising: a. oral administration of docetaxel at an amount of about 15 mg/m² to about 450 mg/m² to the subject once a day and for 1-7 times a week; and b. oral administration of Compound A:

to the subject once a day and for 1-7 times a week, wherein the plasma exposure of the orally administered docetaxel, as measured by AUC_((0→∞)), is equal to or greater than the plasma exposure, as measured by AUC_((0→∞)), of intravenously administered docetaxel at an amount of about 30 mg/m² to 100 mg/m² over a period of about 1 to about 24 hours once every three weeks, once every two weeks, or once every week, and wherein Compound A is administered simultaneously with or prior to the docetaxel.
 130. A method for reducing or preventing hypersensitivity-type infusion reactions associated with intravenously administered docetaxel therapy in a subject suffering from cancer, comprising: a. oral administration of docetaxel at an amount of about 15 mg/m² to about 450 mg/m² to the subject once a day and for 1-7 times a week; and b. oral administration of Compound A:

to the subject once a day and for 1-7 times a week; wherein the orally administered docetaxel reaches therapeutic blood or plasma levels in the subject, and wherein Compound A is administered simultaneously with or prior to the docetaxel. 131.-139. (canceled)
 140. The method of claim 128, wherein the docetaxel is administered as a single dose.
 141. The method of claim 128, wherein the docetaxel is administered at an amount of about 75 mg/m² to about 350 mg/m².
 142. The method of claim 128, wherein Compound A or a pharmaceutically acceptable salt or solvate thereof is administered orally at an amount of about 15 mg to about 50 mg.
 143. The method of claim 128, wherein the cancer is breast cancer.
 144. The method of claim 128, wherein the cancer is pancreatic cancer.
 145. The method of claim 128, wherein the cancer is non-small cell lung cancer.
 146. The method of claim 128, wherein the cancer is ovarian cancer.
 147. The method of claim 128, wherein the cancer is esophageal cancer.
 148. The method of claim 128, wherein the cancer is endometrial cancer.
 149. The method of claim 128, wherein the cancer is cervical cancer.
 150. The method of claim 128, wherein the cancer is urothelial cancer.
 151. The method of claim 128, wherein the cancer is prostate cancer.
 152. The method of claim 128, wherein Compound A or a pharmaceutically acceptable salt or solvate thereof is administered before the docetaxel is administered.
 153. The method of claim 128, wherein Compound A or a pharmaceutically acceptable salt or solvate thereof and the docetaxel are administered on the same day.
 154. The method of claim 128, comprising oral administration of docetaxel once per week.
 155. The method of claim 128, comprising oral administration of docetaxel at least twice per week.
 156. The method of claim 128, comprising oral administration of docetaxel once over a three-week period. 